Silicon-incorporated ionizable cationic lipids

Abstract

The present invention relates to a family of novel silicon-incorporated, ionizable cationic lipids, belonging to the LipexSil™ first-generation lipid family, in which at least one of the two side chains contains a silyl acetal linker. Lipids containing silyl acetal linkers are unprecedented in the art and are effective as ionizable cationic lipids in the formulation of empty or loaded lipid nanoparticles (LNPs). The novel linkers according to the present invention are designed by borane catalysis [WO 2022 / 129966]. The present invention describes the synthesis of lipids of formula (I), nanoparticle formation and characterization, and biological experiments demonstrating that lipid nanoparticles prepared using these novel lipids can efficiently deliver their cargo (e.g., RNA, DNA, mRNA, siRNA, pDNA, circular DNA, and biologically active small molecules) into cells.

Description

[Technical Field]

[0001] The present invention is in the field of biomedicine and drug delivery.

[0002] The present invention relates to a family of novel silicon-incorporated, ionizable cationic lipids, belonging to the LipexSil™ first-generation lipid family, in which at least one of the two side chains contains a silyl acetal linker. Lipids containing silyl acetal linkers are unprecedented in the art and are effective as ionizable cationic lipids in the formulation of empty or loaded lipid nanoparticles (LNPs). The novel linkers according to the present invention are designed by borane catalysis [WO 2022 / 129966]. The present invention describes the synthesis of lipids of formula (I), nanoparticle formation and characterization, and biological experiments demonstrating that lipid nanoparticles prepared using these novel lipids can efficiently deliver their cargo (e.g., RNA, DNA, mRNA, siRNA, pDNA, circular DNA, and biologically active small molecules) into cells. [Background technology]

[0003] Many challenges exist regarding the transfection of nucleic acid-based drugs, such as messenger RNA, antisense oligonucleotides, ribozymes, plasmids, and small molecules, to elicit desired responses in biological systems. The design and synthesis of novel second-generation lipids (biodegradable, ionizable amine lipids) is needed to improve the cellular delivery of bioactive agents, such as DNA, RNA, mRNA, and various small molecules. In the field of medicine, these treatments are most effective when they can selectively and directly target diseased cells or tissues with appropriate drug substances. With this in mind, therapeutic efficacy should be enhanced while avoiding or reducing unwanted toxic side effects. Loaded lipid nanoparticles (LNPs) containing lipid components have proven to be effective carrier systems that can be functionalized for payload protection and delivery to target sites. It should be emphasized that LNPs formed from ionizable cationic lipids have also proven to be excellent lipid-based carriers for gene therapy.

[0004] LNPs also contain synthetic lipids that can be toxic to human cells, and the cytotoxicity of synthetic lipids depends on the specific motifs in the lipids (e.g., head group type, linker) involved in their biodegradability and their metabolic pathways in the human body.

[0005] LNPs have several key parameters that play a major role in successful drug delivery applications, including particle size, polydispersity index (PDI), zeta potential, and apparent pKa. Based on literature data, the average particle size of LNPs is typically 100-400 nm with a narrow particle size distribution of <0.2 PDI (Advanced NanoBiomed Research, 2022, 2, 2100109). The optimal apparent pKa of LNPs is 6-7 (Trends in Pharmacological Sciences, 2021, 42:6, 448-460).

[0006] In the art, there are several examples that demonstrate that silicon-containing lipids are also suitable components of LNPs (International Publication Nos. 2011134675, 2021055835), which are effective for the delivery of DNA, RNA, siRNA, nucleotides, etc. Silicon is a carbon isostere in drug research, and the incorporation of silicon atoms can provide innovative solutions to problems in medicinal chemistry. The silicon atoms incorporated in lipids can increase lipophilicity, thereby improving membrane permeability. Nevertheless, as gene therapy becomes part of routine treatment in the next decade, there is still a growing demand in the art for efficient, biodegradable, and low-toxicity delivery platforms. Summary of the Invention

[0007] The present invention provides a series of novel silicon-incorporated lipids having the structure of formula (I), details of the synthesis method, details of the formation and characterization of LNPs, and toxicity and transfection experiments of loaded LNPs. DETAILED DESCRIPTION OF THE INVENTION

[0008] In one embodiment, the present invention provides an ionizable cationic lipid of formula (I): [ka] or a salt or stereoisomer thereof, During the ceremony: G 1 is unsubstituted C2-C9 alkylene, -(CH2) x -CH=CH-(CH2) y - (wherein x is an integer selected from 1 to 6, y is an integer selected from 1 to 6, and the sum of x and y is an integer selected from 2 to 7), or -(CH2) w -X-(CH2) z-(wherein w is an integer selected from 1 to 7, z is an integer selected from 2 to 7, and the sum of w+z is an integer selected from 3 to 8), z - is attached to N and X is selected from O, S, SO and SO; T 1 teeth, [ka] wherein: b 1 is G 1 It is a combination with X1 and X2 are the same or different and each independently represent O or S; R1 in each case optionally contains one S, SO, SO2, O, or Si(R a )2(wherein, R a is a C1-C6 alkyl) at any position within the carbon chain, provided that the heteroatoms are not at the alpha or omega positions of the carbon chain. 17 Alkyl, non-linear C3-C 17 Alkyl, C3-C containing one double bond, provided that there is at least one -CH2- group between the double bond and X2 17 Alkenyl or polyunsaturated C8-C provided that there is at least one -CH2- group between the first double bond and X2 20 alkenyl, or R1 is [ka] where R 17 , R 18 and R 19 are the same or different and each independently may be H, OH, —C1-C6 alkoxy, or fluorine; R2 is In either case, optionally one S, SO, SO2, O, or Si(R b )2(wherein, R bis a C1-C6 alkyl) at any position within the carbon chain, provided that the heteroatoms are not at the alpha or omega positions of the carbon chain. 17 Alkyl, non-linear C3-C 17 Alkyl, C3-C containing one double bond, provided that there is at least one -CH2- group between the double bond and the carbon connecting X1 and X2 17 Alkenyl or polyunsaturated C8-C provided that there is at least one -CH2- group between the first double bond and the carbon connecting X1 and X2 20 alkenyl, or R2 is [ka] where R 20 , R 21 and R 22 are the same or different and each independently may be H, OH, —C1-C6 alkoxy, or fluorine; However, R1 and R2 are both simultaneously [ka] and [ka] provided that it cannot be, or R1 is connected to R3 via alkylene or monounsaturated alkenyl and has a C5-C 30 form a membered ring, or R2 is connected to R3 via alkylene or monounsaturated alkenyl and has a C5-C 30 forming a 1-membered ring, wherein the first or second carbon atom of R, numbered from the carbon atom attached to the carbon connecting X and X, is optionally replaced by an O or S heteroatom; or R2 is connected to R1 via alkylene or monounsaturated alkenyl and has a C5-C30 forming a 1-membered ring, wherein the first or second carbon atom of R, numbered from the carbon atom attached to the carbon connecting X and X, is optionally replaced by an O or S heteroatom; R3 is [ka] and R5-b 1 teeth, [ka] where: b 2 is the bond to X1, Y1 is -O- or -CH2- or -O-CH2-CH2-, where -CH2- is bonded to Si; each X3 is independently selected from the group consisting of C1-C4 alkyl or C1-C4 alkoxy; R4 in each case optionally contains one S, SO, SO2, O, or Si(R c )2(wherein, R c is a C1-C6 alkyl) at any position within the carbon chain, provided that the heteroatoms are not at the alpha or omega positions of the carbon chain. 17 Alkyl or non-linear C3-C 17 Alkyl, C3-C containing one double bond, provided that there is at least one -CH2- group between the double bond and Y1 20 Alkenyl or polyunsaturated C8-C provided that there is at least one -CH2- group between the first double bond and Y1 20 alkenyl, or R 4 teeth, [ka] where b 3 is the bond with Y1, R6, R7, and R8 are the same or different and may each independently represent H, OH, —C1-C6 alkoxy, or fluorine; D 1 teeth, [ka] wherein: b 4 is the bond to nitrogen, R9 is C1-C6 alkyl, cyclopentyl, cyclohexyl, hydroxyl, hydroxymethyl, hydroxyethyl, phenyl, benzyl, 4-hydroxybenzyl, [ka] may be R 10 and R 11 is independently selected from H and C1-C6 alkyl; m is an integer selected from 1 to 6; n is an integer selected from 0 to 6, o is an integer selected from 0 to 6; p is an integer selected from 2 to 6; q is an integer selected from 0 to 6, j is an integer selected from 1 to 4, Cy1 is a C3-C6 cycloalkyl optionally substituted with one or more -OH; or Cy1 is a pyranose or furanose ring that can be linked via any of its OH groups and is optionally substituted by an -NH-CO-CH3 group, adenine, guanine, uracil, cytosine, thymine, a mono- or oligosaccharide, or a 4-, 5-, 6- or 7-membered heterocycle containing 1, 2, 3 or 4 heteroatoms selected from N, O or S, or Cy1 is a 4-, 5-, 6-, or 7-membered heterocycle containing 1, 2, 3, or 4 heteroatoms selected from O, N, or S, wherein the heterocycle is optionally12 is replaced by where: R 12 represents a C1-C6 alkyl, an arginine-containing peptide, a pyranose or furanose ring linked by any of its ring carbon atoms to a 4-, 5-, 6- or 7-membered heterocycle, and optionally substituted with an -NH-CO-CH3 group, adenine, guanine, uracil, cytosine, thymine, or a mono- or oligosaccharide; R 12 may be a group selected from (d), (e), or (f), where b 4 is a bond to a heterocycle, and m, n, o, p, R9, R 10 and R 11 is as defined above, or R 12 teeth, [ka] wherein r is an integer selected from 1 to 4; and Cy2 is a 4-, 5-, 6-, or 7-membered heterocycle containing 1, 2, 3, or 4 heteroatoms selected from O, N, and S, optionally substituted with C1-C6 alkyl; P is (i)G 2 -T 2 [In the formula, G 2 is the above G 1 where G 1 and G 2 may be the same or different, T 2 is the above T 1 It is defined as b 1 is G 2 and T 1 and T 2 may be the same or different], or (ii) G 2 -T 3 [In the formula, G 2 is as defined above, T 3 teeth, [ka] wherein: b 5 is G 2 It is a combination with X4 and X5 may be the same or different and each independently represent O, S, or NR d where R d is H, C1-C6 alkyl, —OH or C1-C6 alkoxy, R 13 are both optionally S, SO, SO2, O, Si(R e )2(wherein, R e is a C1-C6 alkyl) at any position within the carbon chain, provided that the heteroatom is not at the alpha or omega position of the carbon chain. 17 Alkyl, non-linear C3-C 17 Alkyl, C3-C containing one double bond, provided that there is at least one -CH2- group between the double bond and X5 20 Alkenyl or polyunsaturated C8-C provided that there is at least one -CH2- between the first double bond and X5 20 alkenyl, or R 13 teeth, [ka] where R 23 , R 24 , R 25 are the same or different and may each independently be H, OH, —C1-C6 alkoxy, or fluorine; R 14 are both optionally S, SO, SO2, O, Si(R f )2(wherein, R fis a C1-C6 alkyl) at any position within the carbon chain, provided that the heteroatom is not at the alpha or omega position of the carbon chain. 17 Alkyl, non-linear C3-C 17 Alkyl, C3-C containing one double bond, provided that there is at least one -CH2- group between the double bond and the carbon connecting X4 and X5 20 Alkenyl or polyunsaturated C8-C provided that there is at least one -CH2- between the first double bond and the carbon connecting X4 and X5 20 alkenyl, or R 14 teeth, [ka] where R 26 , R 27 , R 28 are the same or different and may each independently be H, OH, —C1-C6 alkoxy, or fluorine; and (iii) T 4 [In the formula, T 4 teeth, [ka] where b 6 is a bond to a nitrogen atom, and R 29 , R 30 , R 31 may be the same or different, and each independently represents H, OH, -C1 to C6 alkoxy or fluorine, C4-C containing one double bond, provided that there is at least one -CH2- between the double bond and the N 20 alkenyl, or Polyunsaturated C8-C provided that there is at least one -CH2- between the first double bond and the N 20 may be alkenyl].

[0009] Unsubstituted C2 to C9 alkylene means ethylene (-(CH2)2-), propylene (-(CH2)3-), butylene (-(CH2)4-), pentylene (-(CH2)5-), hexylene (-(CH2)6-), heptylene (-(CH2)7-), octylene (-(CH2)8-), or nonylene (-(CH2)9-).

[0010] Linear C1~C 17 Alkyl means methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyltridecyl, tetradecyl, pentadecyl, hexadecyl, or heptadecyl.

[0011] Non-linear C3~C 17 Alkyl means a saturated branched alkyl group containing 3 to 17 carbon atoms, for example, isopropyl, isobutyl, 3-methylpentyl, 2-propylpentyl, 2-methylhexyl, 2-ethylhexyl, 2-ethyldecyl, 2-propyldecyl, 2-butyldecyl, 2-pentyldecyl, 2-hexyldecyl, or 2-heptyldecyl.

[0012] A C1-C6 alkyl group means a linear or non-linear alkyl group containing 1 to 6 carbon atoms, such as methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl, isobutyl, tert-butyl, neopentyl, isopentyl, neohexyl or isohexyl, preferably methyl or ethyl.

[0013] By C1-C4 alkyl group is meant a linear or non-linear alkyl group containing 1 to 4 carbon atoms, preferably methyl.

[0014] Straight-chain C1-C alkyls, both of which contain one S, SO, SO2, O, or Si(R)2 (where R is a C1-C6 alkyl as defined above) anywhere within the carbon chain, provided that the heteroatoms are not at the alpha or omega positions of the carbon chain. 17 Alkyl or non-linear C3-C 17Alkyl refers to a linear C1-C1 alkyl group as defined above, in which one -CH2- of the alkyl chain, not at the end of any side of the chain, is replaced by one of the following groups: -O-, -S-, -SO-, SO2-, -Si(R)2-. 17 Alkyl or non-linear C3-C 17 It means alkyl.

[0015] C3-C containing one double bond 17 Alkenyl or C3-C containing one double bond 20 Alkenyl means a straight-chain or non-straight-chain alkyl group as defined above containing one double bond in the chain and containing 3 to 17 or 3 to 20 carbon atoms, respectively, such as hex-3-en-1-yl, oct-3-en-1-yl, dec-3-en-1-yl, dec-2-en-1-yl, undec-3-en-2-yl, preferably hex-3-en-1-yl, oct-3-en-1-yl.

[0016] C1-C6 alkoxy means an -O-C1-C6 alkyl group, wherein the C1-C6 alkyl group is as defined above.

[0017] C1-C4 alkoxy means an -O-C1-C4 alkyl group, wherein the C1-C4 alkyl group is as defined above, such as methoxy, ethoxy, propoxy, butoxy, isopropoxy, sec-butoxy or tert-butoxy.

[0018] C5-C connected to R3 via alkylene or monounsaturated alkenyl 30 R1 forming a membered ring means, for example, the following: [ka]

[0019] C5-C connected to R3 via alkylene or monounsaturated alkenyl 30R2 forming a 1-membered ring, wherein the first or second carbon atom of R2, numbered from the carbon atom attached to the carbon connecting X1 and X2, can be optionally replaced by an O or S heteroatom, R2 means, for example: [ka]

[0020] C5-C connected to R1 via alkylene or monounsaturated alkenyl 30 R2 forming a 1-membered ring, wherein the first or second carbon atom of R2, numbered from the carbon atom attached to the carbon connecting X1 and X2, can be optionally replaced by an O or S heteroatom, R2 means, for example: [ka]

[0021] Polyunsaturated C8-C 20 Alkenyl refers to groups having multiple isolated double bonds within the chain, preferably groups derived from omega-3 and omega-6 fatty acids, such as T, R, or R 13 The following groups in: [ka] and R2 or R 14 The following groups in: [ka] where the group is attached via b and represents a linear alkyl chain containing 8 to 20 carbon atoms.

[0022] C3-C6 cycloalkyl means, for example, cyclopropyl, cyclopentyl, or cyclohexyl.

[0023] A 4-, 5-, 6-, or 7-membered heterocycle containing 1, 2, 3, or 4 heteroatoms selected from N, O, or S refers to an aromatic ring or an unsaturated, partially saturated, or fully saturated heterocycle, such as azetine, azetidine, pyrrolidine, oxazolidine, piperidine, piperazine, morpholine, pyrrole, imidazole, pyrazole, 1,2,3-triazole, 1,2,4-triazole, tetrazole, pyridine, pyrimidine, pyridazine, pyrazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,4,5-tetrazine, oxazole, isoxazole, thiazole, isothiazole, 1,2-oxazine, 1,3-oxazine, 1,4 -oxazine, 1,2-thiazine, 1,3-thiazine, 1,4-thiazine, azepane, azepine, 1,2-diazepane, 1,3-diazepane, 1,4-diazepane, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine, 1,2-oxazepane, 1,3-oxazepane, 1,4-oxazepane, 1,2-oxazepine, 1,3-oxazepine, 1,4-oxazepine, 1,2-thiazepane, 1,3-thiazepane, 1,4-thiazepane, 1,2-thiazepine, 1,3-thiazepine or 1,4-thiazepine ring, preferably pyrrolidine, imidazole, 1,2,3-triazole, piperidine, piperazine or morpholine.

[0024] By furanose is meant all stereoisomers of ribofuranose, deoxyribofuranose, xylofuranose, fructofuranose, glucofuranose, galactofuranose, mannofuranose, allofuranose, arabinofuranose, or altrofuranose, which may also be protected, for example, by acetyl, benzyl, benzoyl, isopropylidene, or benzylidene groups (e.g., 2,3,5,6-tetra-O-acetyl-galactofuranose).

[0025] By pyranose is meant all stereoisomers of glucopyranose, galactopyranose, mannopyranose, allopyranose, fructopyranose, arabinopyranose or altropyranose, which may also be protected, for example, by acetyl, benzyl, benzoyl, isopropylidene or benzylidene groups (for example: 2,3,4,6-tetra-O-acetyl-glucopyranose).

[0026] By monosaccharides is meant monosaccharides as defined above, and by oligosaccharides is meant oligosaccharides such as sucrose, lactose, maltose, isomaltulose, cellobiose, trehalose.

[0027] An arginine-containing peptide refers to a peptide having six or fewer amino acids that includes at least one arginine residue. The peptides are linked by their C- or N-terminus.

[0028] The salt of the compound of formula (I) means a salt of the compound of formula (I) with an inorganic or organic acid. Preferred salts are those with pharmaceutically acceptable acids. The salts are, for example, chloride, sulfate, phosphate, formate, acetate, fumarate, maleate, oxalate, citrate or tartrate. Salts formed during purification or isolation are also subject of the present invention.

[0029] Stereoisomers refer to optical isomers and geometric isomers.The compound of formula (I) may contain one or more asymmetric carbon atoms, and therefore can exist in the form of optical isomers, enantiomers or diastereomers.The compound of formula (I) may contain double bonds, and the groups attached to the double bonds can have different (cis or trans) conformations, for example, cis or trans fatty acid moieties.

[0030] Particular groups of compounds of formula (I) are as follows: G 1 is unsubstituted C2-C9 alkylene, -(CH2) x -CH=CH-(CH2) y- (wherein x is an integer selected from 1 to 6, y is an integer selected from 1 to 6, and the sum of x and y is an integer selected from 2 to 7), or -(CH2) w -X-(CH2) z -(wherein w is an integer selected from 1 to 7, z is an integer selected from 2 to 7, and the sum of w+z is an integer selected from 3 to 8), z - is attached to N and X is selected from O, S, SO and SO; T 1 teeth, [ka] wherein: b 1 is G 1 It is a combination with X1 and X2 are the same or different and each independently represent O or S; R1 in each case optionally contains one S, SO, SO2, O, or Si(R a )2(wherein, R a is a C1-C6 alkyl) at any position within the carbon chain, provided that the heteroatoms are not at the alpha or omega positions of the carbon chain. 17 Alkyl, non-linear C3-C 17 Alkyl, C3-C containing one double bond, provided that there is at least one -CH2- group between the double bond and X2 17 Alkenyl or polyunsaturated C8-C provided that there is at least one -CH2- group between the first double bond and X2 20 is alkenyl, R2 in each case optionally contains one S, SO, SO2, O, or Si(R b )2(wherein, R b is a C1-C6 alkyl) at any position within the carbon chain, provided that the heteroatoms are not at the alpha or omega positions of the carbon chain. 17Alkyl, non-linear C3-C 17 Alkyl, C3-C containing one double bond, provided that there is at least one -CH2- group between the double bond and the carbon connecting X1 and X2 17 Alkenyl or polyunsaturated C8-C provided that there is at least one -CH2- group between the first double bond and the carbon connecting X1 and X2 20 is alkenyl, R3 is [ka] and R5-b 1 teeth, [ka] where: b 2 is the bond to X1, Y1 is -O- or -CH2- or -O-CH2-CH2-, where -CH2- is bonded to Si; each X3 is independently selected from the group consisting of C1-C4 alkyl or C1-C4 alkoxy; R4 in each case optionally contains one S, SO, SO2, O, or Si(R c )2(wherein, R c is a C1-C6 alkyl) at any position within the carbon chain, provided that the heteroatoms are not at the alpha or omega positions of the carbon chain. 17 Alkyl or non-linear C3-C 17 Alkyl, C3-C containing one double bond, provided that there is at least one -CH2- group between the double bond and Y1 20 Alkenyl or polyunsaturated C8-C provided that there is at least one -CH2- group between the first double bond and Y1 20 alkenyl, or R 4 teeth, [ka] where b 3 represents a bond to Y1, and R6, R7, and R8 may be the same or different and may each independently represent H, OH, —C1-C6 alkoxy, or fluorine; D 1 teeth, [ka] wherein: b 4 is the bond to nitrogen, R9 may be C1-C6 alkyl, hydroxy, or hydroxymethyl; m is an integer selected from 1 to 6; n is an integer selected from 0 to 6, o is an integer selected from 0 to 6; p is an integer selected from 2 to 6; R 10 and R 11 is independently selected from H and C1-C6 alkyl; q is an integer selected from 0 to 6, Cy1 is a C3-C6 cycloalkyl optionally substituted with one or more -OH; or Cy1 is a pyranose or furanose ring that can be linked via any of its OH groups and is optionally substituted by an -NH-CO-CH3 group, adenine, guanine, uracil, cytosine, thymine, a mono- or oligosaccharide, or a 4-, 5-, 6- or 7-membered heterocycle containing 1, 2, 3 or 4 heteroatoms selected from N, O or S, or Cy1 is a 4-, 5-, 6-, or 7-membered heterocycle containing 1, 2, 3, or 4 heteroatoms selected from O, N, or S, wherein the heterocycle is optionally 12 is replaced by where: R 12represents a C1-C6 alkyl, an arginine-containing peptide, a pyranose or furanose ring linked by any of its ring carbon atoms to a 4-, 5-, 6- or 7-membered heterocycle, and optionally substituted with an -NH-CO-CH3 group, adenine, guanine, uracil, cytosine, thymine, or a mono- or oligosaccharide; R 12 may be a group selected from (d), (e), or (f), where b 4 is a bond to a heterocycle, and m, n, o, p, R9, R 10 and R 11 is as defined above, or R 12 teeth, [ka] wherein r is an integer selected from 1 to 4; and Cy2 is a 4-, 5-, 6-, or 7-membered heterocycle containing 1, 2, 3, or 4 heteroatoms selected from O, N, and S, optionally substituted with C1-C6 alkyl; P is (i)G 2 -T 2 [In the formula, G 2 is the above G 1 where G 1 and G 2 may be the same or different, T 2 is the above T 1 is defined as b 1 is G 2 and T 1 and T 2 may be the same or different], or (ii) G 2 -T 3 [In the formula, G 2 is as defined above, T 3 teeth, [ka] where: b 5 is G 2 It is a combination with X4 and X5 may be the same or different and each independently represent O, S, or NR d where R d is H, C1-C6 alkyl, —OH or C1-C6 alkoxy, R 13 are both optionally S, SO, SO2, O, Si(R e )2(wherein, R e is a C1-C6 alkyl) at any position within the carbon chain, provided that the heteroatom is not at the alpha or omega position of the carbon chain. 17 Alkyl, non-linear C3-C 17 Alkyl, C3-C containing one double bond, provided that there is at least one -CH2- group between the double bond and X5 20 Alkenyl or polyunsaturated C8-C provided that there is at least one -CH2- between the first double bond and X5 20 is alkenyl, R 14 are both optionally S, SO, SO2, O, Si(R f )2(wherein, R f is a C1-C6 alkyl) at any position within the carbon chain, provided that the heteroatom is not at the alpha or omega position of the carbon chain. 17 Alkyl, non-linear C3-C 17 Alkyl, C3-C containing one double bond, provided that there is at least one -CH2- group between the double bond and the carbon connecting X4 and X5 20 Alkenyl or polyunsaturated C8-C provided that there is at least one -CH2- between the first double bond and the carbon connecting X4 and X5 20 alkenyl], and (iii)T4 [In the formula, T 4 teeth, [ka] where b 6 is a bond to the nitrogen atom, and R 29 , R 30 , R 31 may be the same or different, and each independently represents H, OH, -C1 to C6 alkoxy, or fluorine, or C4-C containing one double bond, provided that there is at least one -CH2- between the double bond and the N 20 alkenyl, or Polyunsaturated C8-C provided that there is at least one -CH2- between the first double bond and the N 20 may be alkenyl].

[0031] The narrower group of compounds of formula (I) is 1 and G 2 (if present) are the same or different and each independently represent a straight chain C4 to C9 alkylene, preferably a C5 to C9 alkylene, or each independently represent a straight chain C5, C6, C7, or C9 alkylene.

[0032] Another group of compounds of formula (I) is a compound of formula (I) wherein R1 is a linear C1, C2, C4, C6, C7, C8, C9, C 10 , or C 12 or R1 is a linear C9 alkenyl and / or R2 is a linear C1, C3, C5, C6, C7, C8, C9, or C 11 alkyl, preferably R1 is a linear C2, C8, C 10 alkyl, or R1 is a straight chain C9 alkenyl and / or R2 is a straight chain C1, C3, C7, or C9 alkyl.

[0033] Specific embodiments of this group are those in which T 1is (c), and R1 is a linear C2, C4, C6, C7, C8, C9, C 10 , or C 12 or R1 is a linear C9 alkenyl and R2 is a linear C1, C3, C5, C6, C7, C8, C9, or C 11 alkyl, preferably R1 is a linear C2, C8, C 10 alkyl, or R1 is a straight chain C9 alkenyl and R2 is a straight chain C1, C3, C7, or C9 alkyl.

[0034] Another group of compounds of formula (I) are those in which R4 is a linear C5, C7, C8 alkyl or R4 is a non-linear C 16 It is alkyl.

[0035] Specific embodiments of this group are those in which T 1 is (b).

[0036] A further group of compounds of formula (I) is 2 -T 2 is.

[0037] In particular embodiments of that group, G 1 -T 1 and G 2 -T 2 are identical.

[0038] Another group of compounds of formula (I) are those wherein P is G 2 -T 3 is.

[0039] In a particular embodiment of that group, T 1 -G 1 has one of the following structures: [ka]

[0040] The narrower group of compounds of formula (I) is T 3 But the following structure [ka] (In the formula, b 5 is G 2 (which is a bond with

[0041] Another group of compounds of formula (I) are those wherein P is T 4 is.

[0042] In a particular embodiment of that group, T 4 teeth, [ka] (In the formula, b 6 is a bond to a nitrogen atom, and R 29 , R 30 , R 31 may be the same or different and each independently may be H, OH, —C1-C6 alkoxy, or fluorine), or Polyunsaturated C8-C provided that there is at least one -CH2- between the first double bond and the N 20 It is alkenyl.

[0043] In a further particular embodiment of that group, T 4 has the following structure: [ka] (In the formula, b 6 is a bond to a nitrogen atom).

[0044] Another group of compounds of formula (I) is D 1 has one of the following structures: [ka]

[0045] Another group of compounds of formula (I) are those in which D 1 But the following structure: [ka] (wherein q is an integer selected from 1 to 4, and b 4 is a bond to nitrogen).

[0046] In some embodiments, D 1 has one of the following structures: [ka]

[0047] The present invention also provides lipid nanoparticles (LNPs) comprising a compound of formula (I) as defined above and a therapeutic agent (e.g., RNA, DNA, mRNA, siRNA, pDNA, circular DNA, or a biologically active small molecule).

[0048] In certain embodiments, the present invention provides lipid nanoparticles comprising a compound of formula (I) and mRNA (e.g., luciferase or green fluorescent protein (GFP)).

[0049] The present invention also provides a method for delivering mRNA into a cell.

[0050] The present invention opens up a new chemical space through silicon-containing linkers, which lead to novel biodegradable lipids of formula (I). The mentioned linkers are very difficult to synthesize using conventional chemical tools, but the recently published borane catalyst [WO 2022 / 129966] has made their synthesis feasible. The mixed acetal building blocks of the present invention were prepared using a method similar to that described in WO 2022 / 129966. These novel mixed acetals are structurally different from those described in WO 2022 / 129966, and a further difference is that the mixed acetal moiety is retained and incorporated into the lipids according to the present invention.

[0051] Another important feature of the present invention is its modularity: the nature of the designed silicon-based linkers allows for the design and synthesis of large numbers of compounds and diverse lipid libraries from simple and readily available starting materials.

[0052] In addition, the chemical stability (e.g., susceptibility to hydrolysis) of silicon-containing ionizable lipids can be fine-tuned by the chemical properties of the substituents and the number of O and Si atoms on the mixed silyl acetal group (linker), which manifests itself in the biodegradability of the lipid.

[0053] Another aspect of the present invention is the preparation of compounds of formula (I) and intermediates and building blocks used therein.

[0054] Compounds of formula (I) can be prepared according to the following reaction scheme. General Reaction Scheme 1 - Synthesis of Symmetric Lipids [ka]

[0055] General Reaction Scheme 1 shows a reaction of a compound of formula (I) 1 -G 1 and P are the same, X6 is a halogen or pseudohalogen, G 1 , X1, X2, R1, R2, R3, D 1The following examples illustrate methods for making symmetric lipids of the invention having structures A-1, A-1', A-1", A-2, A-2', A-3, A-3', A-3" and A-4, A-4' and A-6. Compounds of structures A-1, A-1', A-1", A-2, A-2', A-3, A-3', A-3" and A-4, A-4' and A-6 may be purchased or prepared according to methods known in the art. Reaction of the carboxylic acid derivative A-1 or A-1′ or A-1″ with the alcohol derivative A-2 or A-2′ under suitable esterification conditions (e.g., oxalyl chloride, EtN) gives the ester A-3 or A-3′ or A-3″, which can be converted to the mixed silyl acetal A-5 or A-5′ or A-5″ using a suitable silane derivative A-4 or A-4′ and a borane catalyst (borane catalysts are disclosed in WO 2022 / 129966). The resulting mixed silyl acetal A-5 or A-5′ or A-5″ corresponding to formula (II) containing a halogen or pseudohalogen atom is reacted with the amine derivative A-6 under suitable alkylation conditions (e.g., KI, KCO in CPME / MeCN) to give the compound A-7 or A-7′ or A-7″, respectively. General Reaction Scheme 2 - Synthesis of Asymmetric Lipids Route A [ka]

[0056] Route A of General Reaction Scheme 2 is a reaction of formula (I) 1 -G 1 and P are different, and P is G 2 -T 3 or T 4 X6 is a halogen or pseudohalogen, and G 1 , X1, X2, R1, R2, R3, D 1The following illustrates a method for producing asymmetric lipids of the present invention having the structure (wherein A-8, A-8', and A-6 are as defined above). Compounds of structure A-8, A-8', and A-6 may be purchased or prepared according to methods known in the art. Reaction of the carboxylic acid derivative A-8 or A-8' with methanol or ethanol (HO-X7) under appropriate esterification conditions (e.g., oxalyl chloride, Et3N) provides the ester A-9 or A-9', which can be converted to the mixed silyl acetal A-10 or A-10' using triethylsilane and a suitable borane catalyst (borane catalysts are disclosed in WO 2022 / 129966). The resulting mixed silyl acetal A-10 or A-10' is converted to an aldehyde (previously or in situ), which is reacted with the appropriate amine derivative A-6 under reductive amination conditions (e.g., NaHB(OAc)3, AcOH) to obtain the intermediate compound A-11 or A-11'. Reaction of intermediate A-11 or A-11′ with mixed silyl acetal A-5 or A-5′ or A-5″ (compounds of formula II) under appropriate alkylation conditions (e.g., KI, KCO in CPME / MeCN) provides compounds A-12 or A-12′ or A-12″. Route B [ka]

[0057] Route B of General Reaction Scheme 2 is a reaction of formula (I) 1 -G 1 and P are different, and P is G 2 -T 2 , G 2 -T 3 or T 4 X6 is a halogen or pseudohalogen, and G 1 , X1, X2, R1, R2, R3, D 1The following illustrates a method for preparing the asymmetric lipid of the present invention having the structure (wherein A-5, A-5', or A-5" corresponds to formula (II) containing a halogen or pseudohalogen, by reacting with an amine derivative A-6 under suitable alkylation conditions (e.g., KI, K2CO3 in CPME / MeCN) to obtain intermediate A-13, A-13', or A-13" having the structure of formula (Ia). The resulting intermediate A-13 or A-13' or A-13" is reacted with A-10 or A-10' converted (previously or in situ) to an aldehyde under suitable reductive amination conditions to give A-14 or A-14' or A-14"; or alternatively, A-13 or A-13' or A-13" is reacted with a silyl acetal A-5 or A-5' or A5" bearing a halogen or pseudohalogen to give A-14 or A-14' or A-14". General Reaction Scheme 3 - Synthesis of Headgroup-Modified Lipids via Click Chemistry [ka]

[0058] General Reaction Scheme 3 shows a reaction of a compound of formula (I) 1 -G 1 and P are the same or different, X6 is a halogen or pseudohalogen, W is Z 1 Depending on the meaning of N3 or ethynyl, G 1 , X1, X2, R1, R2, R3, D 1 , Z 1

[0039] Figure 3 illustrates a method for producing headgroup-modified lipids via click chemistry of the present invention, having the structure A-1, A-2, A-3, A-4, A-15, and A-19 (where A-1 is as defined above). While only one example is demonstrated in Scheme 3, other examples can be similarly derived based on general reaction schemes 1 and 2. Compounds of structures A-1, A-2, A-3, A-4, A-15, and A-19 can be purchased or prepared according to methods known in the art. Reaction of carboxylic acid derivative A-1 with alcohol derivative A-2 under appropriate esterification conditions (e.g., oxalyl chloride, EtN) provides ester A-3, which can be converted to mixed silyl acetal A-5 using an appropriate silane derivative A-4 and a borane catalyst (borane catalysts are disclosed in WO 2022 / 129966). The resulting mixed silyl acetal A-5 containing a halogen or pseudohalogen is reacted with the amine derivative A-15 under suitable alkylation conditions (e.g., KI, K2CO3 in CPME / MeCN) to give compound A-16 (compound of formula (Ib)).

[0059] From the resulting intermediate A-16, compound A-17 (formula (Ic)) can be synthesized by further alkylation as described above, or compound A-18 (formula (Ic)) can be synthesized under appropriate reductive amination conditions (e.g., NaHB(OAc)3, AcOH). Reaction of A-17 or A-18 with A-19 under appropriate click chemistry conditions (e.g., azidosugar, CuBr, PMDT in DMF) gives compound D 1 is (g) and Cy1 is an optionally substituted 1,2,3-triazole ring, to give compounds A-7 or A-12. [Brief explanation of the drawings]

[0060] [Figure 1] Figure 139 Transfection efficacy and toxicity of Example 139 at different doses of GFP mRNA (3.3 to 800 ng mRNA / well): (Experiment based on Method B). [Figure 2]Figure 153 Transfection efficacy and toxicity of Example 153 at different doses of GFP mRNA (3.3 to 800 ng mRNA / well): (experiment based on method B). [Figure 3] Figure 10: Transfection efficacy and toxicity of Example 154 at different doses of GFP mRNA (3.3 to 800 ng mRNA / well): (experiment based on method B). [Figure 4] Figure 155 Transfection efficacy and toxicity of Example 155 at different doses of GFP mRNA (3.3 to 800 ng mRNA / well): (experiment based on method B). [Figure 5] Figure 2. Transfection efficacy and toxicity of Example 206 at different doses of GFP mRNA (3.3 to 800 ng mRNA / well): (experiment based on method B). [Figure 6] Figure 2. Transfection efficacy and toxicity of Example 209 at different doses of GFP mRNA (3.3 to 800 ng mRNA / well): (experiment based on method B). [Figure 7] Figure 2. Transfection efficacy and toxicity of Example 211 at different doses of GFP mRNA (3.3 to 800 ng mRNA / well): (experiment based on method B). [Example]

[0061] example The present invention is illustrated by the following examples, which illustrate but do not limit the invention, and in all cases standard work-up and purification methods known to those skilled in the art can be utilized.

[0062] synthesis Ester synthesis (general procedures A-D) [ka] General Procedure A A three-neck round-bottom flask equipped with a dropping funnel, a drying tube (containing CaCl), and a thermometer was charged with 1 equivalent of acid and diethyl ether (concentration: 1.0 mmol of acid in 0.8 mL of diethyl ether). The solution in the flask was cooled to 0 °C, and 1.10 equivalents of oxalyl chloride was added dropwise. The reaction mixture was allowed to warm to room temperature and stirred overnight. After this time, it was concentrated under reduced pressure to give an oil, which was used in the next step without further purification.

[0063] A three-neck round-bottom flask equipped with a dropping funnel, a drying tube (containing CaCl), and a thermometer was charged with 1.0 equivalent of alcohol, 1.0 equivalent of triethylamine, and dichloromethane (concentration: 1.0 mmol of alcohol in 4.0 mL of dichloromethane). The mixture in the flask was cooled to 0 °C, and a dichloromethane solution of 1.0 equivalent of acyl chloride (concentration: 1.0 mmol of acyl chloride in 1.0 mL of dichloromethane) was added dropwise. The reaction mixture was allowed to warm to room temperature and stirred overnight. The reaction was monitored by TLC (hexane / ethyl acetate 4 / 1, PMA visualization). After overnight, the volatiles were removed under reduced pressure, and the triethylamine hydrochloride was filtered. The filtrate was evaporated onto silica gel under reduced pressure and purified by flash column chromatography.

[0064] General Procedure B A three-neck round-bottom flask equipped with a dropping funnel, a drying tube (containing CaCl), and a thermometer was charged with 1.0 equivalent of acid and diethyl ether (concentration: 1.0 mmol of acid in 0.8 mL of diethyl ether). The solution in the flask was cooled to 0°C, and 1.1 equivalents of oxalyl chloride was added dropwise. The reaction mixture was allowed to warm to room temperature and stirred overnight. After this time, it was concentrated under reduced pressure to give an oil, which was used in the next step without further purification.

[0065] A three-necked round-bottom flask equipped with a dropping funnel, a drying tube (containing CaCl), and a thermometer was charged with 1.0 equivalent of alcohol, 1.0 equivalent of triethylamine, and dichloromethane (concentration: 1.0 mmol of alcohol in 4 mL of dichloromethane). The mixture in the flask was cooled to 0 °C, and a dichloromethane solution of 1.0 equivalent of acyl chloride (concentration: 1.0 mmol of acyl chloride in 1.0 mL of dichloromethane) was added dropwise. The reaction mixture was allowed to warm to room temperature and stirred overnight. The reaction was monitored by TLC (hexane / ethyl acetate 4 / 1, PMA visualization). After overnight, the mixture was concentrated to half its volume, and the precipitated triethylamine hydrochloride was filtered off. The salt was washed with 20 mL of dichloromethane and 50 mL of hexane. The filtrate was evaporated. The residue was taken up in 150 mL of hexane, 30 g of silica gel was added, stirred for 10 minutes, and filtered. The silica gel was rinsed with 2 x 100 ml of hexane, and the filtrate was concentrated under reduced pressure to give the product as an oil.

[0066] General procedure C A three-neck round-bottom flask equipped with a dropping funnel, a drying tube (containing CaCl), and a thermometer was charged with 1.25 equivalents of oxalyl chloride and anhydrous dichloromethane (concentration: 1.0 mmol of oxalyl chloride in 0.41 mL of anhydrous dichloromethane). The solution in the flask was cooled to 0 °C, and 1.0 equivalent of acid was added dropwise. The reaction mixture was allowed to warm to room temperature and stirred overnight. After this time, it was concentrated under reduced pressure to give an oil, which was used in the ester synthesis without further purification.

[0067] A three-neck round-bottom flask equipped with a dropping funnel, a drying tube (containing CaCl), and a thermometer was charged with 1.0 equivalent of alcohol, 1.0 equivalent of triethylamine, and dichloromethane (concentration: 1.0 mmol of alcohol in 4 mL of dichloromethane). The mixture in the flask was cooled to 0 °C, and a dichloromethane solution of 1.0 equivalent of acyl chloride (concentration: 1.0 mmol of acyl chloride in 1.0 mL of dichloromethane) was added dropwise. The reaction mixture was allowed to warm to room temperature and stirred overnight. The reaction was monitored by TLC (hexane / ethyl acetate 9 / 1). After overnight, the volatiles were removed under reduced pressure, and the triethylamine hydrochloride was filtered. The filtrate was evaporated onto silica gel under reduced pressure and purified by flash column chromatography.

[0068] General Procedure D A three-neck round-bottom flask equipped with a dropping funnel, a drying tube (containing CaCl2), and a thermometer was charged with carboxylic acid (1.0 equiv.), alcohol (1.0 equiv.), DMAP (0.5 equiv.), and anhydrous dichloromethane (concentration: 1.0 mmol of carboxylic acid in 8.5 mL of anhydrous dichloromethane). The solution in the flask was cooled to 0 °C, and 2.5 equiv. of DCC in dichloromethane (concentration: 1.0 mmol of DCC in 0.45 mL of anhydrous dichloromethane) was added dropwise. The reaction mixture was then stirred at 0 °C for an additional 1 h and then left stirring at room temperature overnight. The reaction mixture was then diluted with petroleum ether and filtered through a Celite pad. The Celite was washed with petroleum ether, and the filtrates were combined and concentrated under reduced pressure. The crude material was purified by flash column chromatography (0–15% dichloromethane in petroleum ether).

[0069] Ester synthesis example Example 1 Synthesis of octyl 6-bromohexanoate Octyl 6-bromohexanoate was prepared from 6-bromohexanoic acid and 1-octanol according to general procedure A and purified in the following manner: 250 g silica column, eluent: hexane / ethyl acetate 4 / 1. The product was obtained as a yellowish oil: 27.7 g, 90.15 mmol, 87% yield. 1 H NMR (500 MHz, CDCl3) δ 4.08 (t, 2H), δ 3.42 (t, 2H), δ 2.33 (t, 2H), δ 1.89 (p, 2H), δ1.70-1.60 (m, 4H), δ 1.55-1.49 (m, 2H), δ 1.45-1.21 (m, 10H), δ 0.90 (t, 3H)

[0070] Example 2 Synthesis of decyl 6-bromohexanoate Decyl 6-bromohexanoate was prepared from 6-bromohexanoic acid and 1-decanol according to general procedure A and purified in the following manner: 750 g silica column, eluent: 0-20% ethyl acetate in hexanes. The product was obtained as a yellowish oil: 35.0 g, 104.37 mmol, 89% yield. 1 H NMR (500 MHz, benzene-d6) δ 4.03 (t, 2H), δ 2.86 (t, 2H), δ 2.02 (t, 2H), δ 1.48 (p, 2H), δ 1.41-1.34 (m, 4H), δ1.32-1.14 (m, 14H), δ 1.09 (m, 2H), δ 0.90 (t, 3H)

[0071] Example 3 Synthesis of octyl 10-bromodecanoate Octyl 10-bromodecanoate was prepared from 10-bromodecanoic acid and 1-octanol according to general procedure A and purified in the following manner: 250 g silica column, eluent: 0-20% ethyl acetate in hexanes. The product was obtained as a yellowish oil: 20.23 g, 55.67 mmol, 70% yield. 1 H NMR (500 MHz, benzene-d6) δ 4.06 (t, 2H), δ 2.95 (t, 2H), δ 2.19 (t, 2H), δ 1.59 (p, 2H), δ 1.53-1.43 (m, 4H), δ1.31-0.94 (m, 20H), δ 0.88 (t, 3H)

[0072] Example 4 Synthesis of 6-bromohexyl octanoate 6-Bromohexyl octanoate was prepared from octanoic acid and 6-bromo-1-hexanol according to general procedure B. The product was obtained as a yellowish oil: 46.0 g, 149.70 mmol, 90% yield. 1 H NMR (500 MHz, benzene-d6) δ 3.95 (t, 2H), δ 2.89 (t, 2H), δ 2.17 (t, 2H), δ 1.59 (p, 2H), δ 1.40 (p, 2H), δ 1.32 (p, 2H), δ 1.27-1.10 (m, 8H), δ 1.01 (m, 4H), δ 0.85 (t, 3H)

[0073] Example 5 Synthesis of 6-bromohexyldecanoate 6-Bromohexyldecanoate was prepared from decanoic acid and 6-bromo-1-hexanol according to general procedure B. The product was obtained as a yellowish oil: 26.4 g, 78.73 mmol, 75% yield. 1 H NMR (500 MHz, benzene-d6) δ 3.95 (t, 2H), δ 2.89 (t, 2H), δ 2.18 (t, 2H), δ 1.61 (p, 2H), δ 1.40 (p, 2H), δ 1.32 (p, 2H), δ 1.29-1.12 (m, 12H), δ 1.01 (m, 4H), δ 0.89 (t, 3H)

[0074] Example 6 Synthesis of 9-bromononyl octanoate 9-Bromonoyl octanoate was prepared from octanoic acid and 9-bromo-1-nonanol according to general procedure B. The product was obtained as a yellowish oil: 51.42 g, 147.18 mmol, 89% yield. 1H NMR (500 MHz, benzene-d6) δ 4.05 (t, 2H), δ 2.96 (t, 2H), δ 2.18 (t, 2H), δ 1.60 (p, 2H), δ 1.48 (m, 4H), δ1.29-0.92 (m, 18H), δ 0.85 (t, 3H)

[0075] Example 7 Synthesis of octyl octanoate Octyl octanoate was prepared from octanoic acid and 1-octanol according to general procedure B. The product was obtained as a yellowish oil: 37.40 g, 145.85 mmol, 89% yield. 1 H NMR (500 MHz, benzene-d6) δ 4.05 (t, 2H), δ 2.17 (t, 2H), δ 1.59 (m, 2H), δ 1.48 (m, 2H), δ 1.33-1.07 (m, 18H), δ 0.86 (m, 6H)

[0076] Example 8 Synthesis of heptyl octanoate Heptyl octanoate was prepared from octanoic acid and 1-heptanol according to general procedure A. The product was obtained as a yellowish oil: 2.18 g, 8.99 mmol, 77% yield. 1 H NMR (500 MHz, benzene-d6) δ 3.99 (t, 2H), δ 2.22 (t, 2H), δ 1.57-1.49 (m, 4H), δ 1.35-1.10 (m, 16H), δ 0.83-0.79 (m, 6H)

[0077] Example 9 Synthesis of nonyl octanoate Nonyl octanoate was prepared from octanoic acid and 1-nonanol according to general procedure A. The product was obtained as a yellowish oil: 2.03 g, 7.05 mmol, 61% yield. 1H NMR (500 MHz, benzene-d6) δ 3.99 (t, 2H), δ 2.22 (t, 2H), δ 1.57-1.50 (m, 4H), δ 1.29-1.10 (m, 20H), δ 0.83-0.79 (m, 6H)

[0078] Example 10 Synthesis of octyl heptanoate Octyl heptanoate was prepared from heptanoic acid and 1-octanol according to general procedure A. The product was obtained as a yellowish oil: 2.49 g, 10.27 mmol, 86% yield. 1 H NMR (500 MHz, benzene-d6) δ 3.99 (t, 2H), δ 2.22 (t, 2H), δ 1.57-1.50 (m, 4H), δ 1.27-1.10 (m, 16H), δ 0.83-0.79 (m, 6H)

[0079] Example 11 Synthesis of octyl nonanoate Octyl nonanoate was prepared from nonanoic acid and 1-octanol according to general procedure A. The product was obtained as a yellowish oil: 2.62 g, 9.69 mmol, 78% yield. 1 H NMR (500 MHz, benzene-d6) δ 3.99 (t, 2H), δ 2.22 (t, 2H), δ 1.57-1.50 (m, 4H), δ 1.34-1.10 (m, 20H), δ 0.83-0.79 (m, 6H)

[0080] Example 12 Synthesis of hexyl decanoate Hexyl decanoate was prepared from decanoic acid and 1-hexanol according to general procedure A. The product was obtained as a yellowish oil: 2.63 g, 10.26 mmol, 88% yield. 1H NMR (500 MHz, benzene-d6) δ 3.99 (t, 2H), δ 2.22 (t, 2H), δ 1.57-1.48 (m, 4H), δ 1.24-1.12 (m, 18H), δ 0.84-0.79 (m, 6H)

[0081] Example 13 Synthesis of decyl hexanoate Decyl hexanoate was prepared from hexanoic acid and 1-decanol according to general procedure A. The product was obtained as a yellowish oil: 2.77 g, 10.8 mmol, 90% yield. 1 H NMR (500 MHz, benzene-d6) δ 3.99 (t, 2H), δ 2.22 (t, 2H), δ 1.60-1.49 (m, 4H), δ 1.29-1.12 (m, 18H), δ 0.85-0.79 (m, 6H)

[0082] Example 14 Synthesis of octyl octanethioate Octyl octanethioate was prepared from octanoic acid and 1-octanethiol according to general procedure C. The product was obtained as a yellowish oil: 3.38 g, 13.08 mmol, 90% yield. 1 H NMR (500 MHz, benzene-d6) δ 2.79 (t, 2H), δ 2.46 (t, 2H), δ 1.63-1.53 (m, 2H), δ 1.51-1.44 (m, 2H), δ 1.35-1.10 (m, 18H), δ0.83-0.78 (m, 6H)

[0083] Example 15 Synthesis of decyl butanoate Decyl butanoate was prepared from butyryl chloride and 1-decanol according to general procedure A. The product was obtained as a yellowish oil: 3.05 g, 13.36 mmol, 93% yield. 1H NMR (500 MHz, benzene-d6) δ 4.05 (t, 2H), δ 2.27 (t, 2H), δ 1.72-1.57 (m, 4H), δ 1.38-1.20 (br. m, 14H), δ 0.94 (t, 3H), δ 0.87 (t, 3H)

[0084] Example 16 Synthesis of (Z)-non-6-en-1-yl octanoate (Z)-Nona-6-en-1-yl octanoate was prepared from octanoic acid and (Z)-non-6-en-1-ol according to general procedure C. The product was obtained as a yellowish oil: 2.10 g, 7.82 mmol, 85% yield. 1 H NMR (500 MHz, benzene-d6) δ 5.46-5.30 (m, 2H), δ 4.03 (t, 2H), δ 2.17 (t, 2H), δ 2.03-1.91 (m, 4H), δ 1.62-1.55 (m, 2H), δ 1.50-1.42 (m, 2H) δ1.30-1.12 (m, 12H), δ 0.93 (t, 3H), δ 0.85 (t, 3H)

[0085] Example 17 Synthesis of (Z)-non-3-en-1-yl octanoate (Z)-Nona-3-en-1-yl octanoate was prepared from octanoic acid and (Z)-non-3-en-1-ol according to general procedure C. The product was obtained as a yellowish oil: 2.17 g, 8.07 mmol, 88% yield. 1 H NMR (500 MHz, benzene-d6) δ 5.44-5.35 (m, 2H), δ5.27-5.18 (m, 2H), δ 3.95 (t, 2H), δ 2.31-2.13 (m, 4H), δ1.98-1.87 (m, 2H), δ 1.58-1.44 (m, 2H) δ 1.32-1.08 (m, 12H), δ0.82-0.73 (m, 6H)

[0086] Example 18 Synthesis of heptadecan-9-yl 8-bromooctanoate Heptadecan-9-yl 8-bromooctanoate was prepared from 8-bromooctanoic acid and heptadecan-9-ol according to general procedure C. The product was obtained as a yellowish oil: 3.20 g, 6.93 mmol, 13% yield. 1 H NMR (500 MHz, CDCl3) δ4.92-4.84 (m, 1H), δ 3.41 (t, 2H), δ 2.30 (t, 2H), δ1.90-1.84 (m, 2H), δ 1.70-1.20 (br. m, 36H), δ 0.89 (m, 6H)

[0087] Example 19 Synthesis of 6-ethoxy-6-oxohexyl 2-hexyldecanoate Step a) In a 500 mL two-neck flask equipped with a stir bar and reflux condenser, 2-hexyldecanoic acid (44.6 g, 51.0 mL, 1 equivalent, 174 mmol) was dissolved in anhydrous toluene (150 mL) under inert conditions (nitrogen gas). Next, 5 drops of DMF and thionyl chloride (51.7 g, 31.7 mL, 2.5 equivalents, 435 mmol) were added under stirring. The reaction mixture was stirred at room temperature until gas evolution slowed (approximately 2 hours). The mixture was then heated to 80-90 °C and stirred for an additional 2 hours until gas evolution ceased. The reaction was monitored by TLC.

[0088] Step b) The solvent and residual thionyl chloride were then removed in vacuo, and the resulting crude product was used in the next reaction step without further purification. In a 500 mL two-neck flask equipped with a stirrer, condenser, and dropping funnel, ethyl 6-hydroxyhexanoate (26.4 g, 26.8 mL, 1 equivalent, 165 mmol) was dissolved in 100 mL of anhydrous toluene under inert conditions (nitrogen gas). Next, triethylamine (25.0 g, 34.5 mL, 1.5 equivalents, 248 mmol) was added, followed by the dropwise addition of 2-hexyldecanoyl chloride (47.8 g, 1.05 equivalents, 174 mmol) dissolved in 60 mL of anhydrous toluene. Precipitation of the resulting TEA-HCl immediately began. The reaction was monitored by TLC, and stirring was continued overnight (16 h) at room temperature. The reaction mixture was then filtered through Celite and washed with additional toluene. The resulting clear solution was washed with 1 M aqueous HCl, followed by saturated NaHCO (aq) and saturated NaCl (aq). The extracted organic phase was dried over MgSO, filtered, and concentrated in vacuo to give 73.2 g of crude product. The ester was purified using column chromatography on silica gel with hexane and ethyl acetate as eluents to give 6-ethoxy-6-oxohexyl 2-hexyldecanoate (58.50 g, 147 mmol, 89% cumulative yield for two reaction steps). 1 H NMR (500 MHz, CDCl3) δ4.16-4.12 (q, 2H), δ 4.08 (t, 2H), δ 2.33-2.30 (m, 2H), δ1.71-1.54 (m, 6H), δ 1.48-1.37 (m, 4H), δ 1.34-1.20 (br. m, 24H), δ 0.89 (t, 6H) Example 20 Synthesis of 6-methoxy-6-oxohexyl 2-(decylthio)hexanoate [ka]

[0089] Step a) A heat-dried 500 mL three-neck round-bottom flask was purged with a stream of argon. The flask was equipped with a dropping funnel, a thermometer, and an argon balloon and charged with 2-bromohexanoic acid (10.00 g, 51.27 mmol) and 300 mL of anhydrous tetrahydrofuran. The reaction mixture was cooled to 0 °C. KOtBu (16.51 g, 147.13 mmol) was added in small portions while maintaining the internal temperature at 0 °C. After stirring at 0 °C for 1 h, 1-decanethiol (12.06 g, 69.21 mmol) was added dropwise while maintaining the internal temperature at 0 °C. The reaction mixture was stirred overnight at room temperature. The reaction was monitored by TLC (hexane / ethyl acetate 4:1, PMA visualization), and after stirring overnight, nearly complete conversion was detected. 250 mL of 1 N HCl solution was then added to the reaction mixture, which was then extracted with 3 x 250 mL of hexane. The combined organic phase was washed with 3 × 100 ml of brine, dried over MgSO, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography with gradient elution (0–20% EtOAc in n-hexane) to give 2-(decylthio)hexanoic acid (12.46 g, 43.19 mmol, 84% yield) as a yellowish oil. 1 H NMR (500 MHz, DMSO-d6) δ 3.15 (t, 1H), δ 2.56 (m, 2H), δ 1.78-1.67 (m, 1H), δ 1.58-1.45 (m, 3H), δ1.39-1.17 (m, 18H), δ 0.86 (t, 6H)

[0090] Step b) 6-Methoxy-6-oxohexyl 2-(decylthio)hexanoate was prepared from 2-(decylthio)hexanoic acid and methyl 6-hydroxyhexanoate according to general procedure C and purified in the following manner: 250 g silica column, eluent: 0-10% ethyl acetate in hexane. The product was obtained as a brown oil: 10.77 g, 25.85 mmol, 79% yield. 1H NMR (500 MHz, benzene-d6) δ 4.00 (m, 2H), δ 3.33 (s, 3H), δ 3.27 (t, 1H), δ 2.74-2.65 (m, 1H), δ2.64-2.55 (m, 1H), δ 2.02 (t, 3H), δ 1.75 (m, 1H), δ 1.58 (m, 2H), δ 1.5-1.1 (m, 24H), δ 0.90 (t, 3H), δ 0.80 (t, 3H) Example 21 Synthesis of 6-methoxy-6-oxohexyl 2-(pentylthio)decanoate [ka]

[0091] Step a) A heat-dried 250 mL three-neck round-bottom flask was purged with a stream of argon. The flask was equipped with a dropping funnel, a thermometer, and an argon balloon and charged with 2-bromodecanoic acid (6.80 g, 27.07 mmol), 1-pentanethiol (3.81 g, 36.55 mmol), and 60 mL of anhydrous tetrahydrofuran. The reaction mixture was cooled to 0 °C. KOtBu (8.72 g, 77.7 mmol) in 80 mL of anhydrous THF was added dropwise while maintaining the internal temperature at 0 °C. The reaction mixture was further stirred overnight at room temperature. The reaction was monitored by TLC (hexane / ethyl acetate 4:1, PMA visualization), and after overnight, nearly complete conversion was detected. Next, 150 mL of 1 N HCl solution was added to the reaction mixture, which was then extracted with 3 x 150 mL of hexane. The combined organic phase was washed with 2 × 150 ml of brine, dried over MgSO, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography with gradient elution (0–20% EtOAc in n-hexane) to give 2-(pentylthio)decanoic acid (6.20 g, 22.59 mmol, 83% yield) as a yellowish oil. 1H NMR (500 MHz, DMSO-d6) δ 3.16 (t, 1H), δ 2.56 (m, 2H), δ 1.77-1.66 (m, 1H), δ 1.58-1.44 (m, 3H), δ1.41-1.14 (m, 16H), δ 0.85 (t, 6H)

[0092] Step b) 6-Methoxy-6-oxohexyl 2-(pentylthio)decanoate was prepared from 2-(pentylthio)decanoic acid and methyl 6-hydroxyhexanoate according to general procedure C and purified in the following manner: 250 g silica column, eluent: 0-10% ethyl acetate in hexane. The product was obtained as a brown oil: 9.37 g, 23.27 mmol, 75% yield. 1 H NMR (500 MHz, benzene-d6) δ 4.00 (m, 2H), δ 3.33 (s, 3H), δ 3.30 (t, 1H), δ 2.71-2.64 (m, 1H), δ 2.61-2.53 (m, 1H), δ 2.02 (t, 3H), δ 1.78 (m, 1H), δ 1.55 (m, 2H), δ 1.48-1.32 (m, 6H), δ1.32-1.07 (m, 16H), δ 0.88 (t, 3H), δ 0.81 (t, 3H)

[0093] Example 22 Synthesis of methyl (4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentanoate Under a stream of argon, a 1000 ml pressure flask was charged with lithocholic acid (5.00 g, 13.30 mmol), 240 ml of anhydrous acetonitrile, cesium carbonate (9.53 g, 29.26 mmol), and methyl iodide (8.30 g, 58.52 mmol). The flask was sealed, and the reaction mixture was heated to 110° C. for 24 hours. The reaction mixture was then cooled, and 20 ml of sodium sulfite (10 wt. %) solution and 200 ml of water were added. The mixture was extracted with 3×200 ml of ethyl acetate. The combined organic phase was washed with 1×100 ml of brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography with gradient elution (5–20% ethyl acetate in hexanes) to give the product as a white solid, methyl (4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentanoate (1.30 g, 3.21 mmol, 24% yield). 1 H NMR (500 MHz, benzene-d6) δ 3.40 (s, 3H), δ 3.38 (t, 3H), δ2.32-2.23 (m, 1H), δ 2.20-2.10 (m, 1H), δ 1.95-1.83 (m, 2H), δ1.83-1.70 (m, 3H), δ 1.67-1.54 (m, 3H), δ 1.53-086 (m, 19H), δ 0.84 (d, 3H), δ 0.74 (s, 3H), δ 0.52 (s, 3H)

[0094] Example 23 Synthesis of undecyl 6-bromohexanoate Undecyl 6-bromohexanoate was prepared from 6-bromooctanoic acid and 1-undecanol according to general procedure C. The product was obtained as a yellowish oil: 27.95 g, 80 mmol, 78% yield. 1H NMR (500 MHz, DMSO-d6) δ 4.01 (t, 2H), δ 3.52 (t, 2H), δ 3.52 (t, 2H), δ 2.30 (t, 2H), δ 1.85-1.78 (m, 2H), δ1.58-1.52 (m, 4H), δ 1.42-1.38 (m, 2H), δ 1.33-1.20 (br. m, 14H), δ 0.87 (t, 3H)

[0095] Example 24 Synthesis of 4-chlorobutyl (9Z,12Z)-octadeca-9,12-dienoate 4-Chlorobutyl (9Z,12Z)-octadeca-9,12-dienoate was prepared from (9Z,12Z)-octadeca-9,12-dienoic acid and 4-chlorobutan-1-ol according to general procedure D. The product was obtained as a yellowish oil: 1.20 g, 3.23 mmol, 45% yield. 1 H NMR (500 MHz, benzene-d6) δ 5.41-5.27 (m, 4H), δ 4.1 (t, 2H), δ 3.58 (t, 2H), δ 2.27 (t, 2H), δ 2.29 (t, 2H), δ 2.08-2.00 (m, 4H), δ1.86-1.78 (m, 4H), δ 1.64-1.59 (m, 2H), δ 1.37-1.25 (m, 14H), δ 0.88 (t, 3H)

[0096] Example 25 Synthesis of 4-chlorobutyl (4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentanoate 4-Chlorobutyl (4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentanoate was prepared from (4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentanoic acid and 4-chlorobutan-1-ol according to general procedure D. The product was obtained as a colorless oil: 2.75 g, 5.72 mmol, 81% yield. 1 H NMR (500 MHz, CDCl3) δ4.12-4.07 (m, 2H), δ 3.56 (t, 2H), δ 3.34 (s, 3H) δ3.21-3.11 (m, 1H), δ 2.40-2.29 (m, 1H), δ 2.26-2.14 (m, 1H), δ1.92-1.51 (br. m, 14H), δ 1.49-0.99 (br. m, 16H), δ 0.91-0.89 (m, 6H), δ 0.63 (s, 3H) Silane synthesis example Example 26 Synthesis of dimethyl(octyl)silane [ka]

[0097] A heat-dried 250 mL three-neck round-bottom flask was purged with a stream of argon. The flask was equipped with a septum, thermometer, and argon balloon and charged with chloro(dimethyl)octylsilane (20.00 g, 96.70 mmol) and 100 mL of anhydrous diethyl ether. The reaction mixture was cooled to 0°C, and lithium aluminum hydride (3.38 g, 88.96 mmol) was added in small portions over 6 hours, maintaining the internal temperature between 0 and 5°C. The reaction was stirred overnight at room temperature. The reaction mixture was then cooled again to 0°C and quenched with a mixture of 30 mL of water and 50 mL of 5% w / w NaOH solution, maintaining the internal temperature below 5°C. Additional water (30 mL) was then added and allowed to warm to room temperature. The phases were separated, and the organic phase was washed with 25 mL of water and dried over MgSO4. After filtering the MgSO4, the volatiles were evaporated under reduced pressure to give the product as a colorless oil dimethyl(octyl)silane (14.40 g, 83.53 mmol, 86% yield). 1 H NMR (500 MHz, CDCl3) δ 3.85 (m, 1H), δ 1.25 (m, 12H), δ 0.90 (t, 3H), δ 0.59 (m, 2H), δ 0.08 (d, 6H) Example 27 Synthesis of dimethyl(hexyl)silane [ka]

[0098] A 250 mL, heat-dried, three-necked round-bottom flask was purged with a stream of argon. The flask was equipped with a thermometer, a condenser, and an argon balloon and charged with chlorodimethylsilane (10.00 g, 105.69 mmol), 1-hexene (8.09 g, 96.17 mmol), Karstedt's catalyst (0.111 mL of 2% Pt in xylene solution), and 100 mL of anhydrous tetrahydrofuran. The reaction mixture was refluxed for 5 hours. The reaction was monitored by GC, and complete conversion was detected after 5 hours of reaction time. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to give chloro(hexyl)dimethylsilane as a colorless oil (15.60 g, 87.26 mmol, 83% yield).

[0099] A heat-dried 250 mL three-neck round-bottom flask was purged with a stream of argon. The flask was equipped with a septum, thermometer, and argon balloon and charged with chloro(dimethyl)hexylsilane (15.60 g, 87.26 mmol) and 90 mL of anhydrous diethyl ether. The reaction mixture was cooled to 0°C, and lithium aluminum hydride (3.05 g, 80.28 mmol) was added in small portions over 5 hours, maintaining the internal temperature between 0 and 5°C. The reaction was stirred at room temperature for an additional hour. The reaction mixture was then cooled again to 0°C and quenched with a mixture of 30 mL of water and 50 mL of 5% w / w NaOH solution, maintaining the internal temperature below 5°C. Additional water (30 mL) was then added and allowed to warm to room temperature. The phases were separated, and the organic phase was washed with 25 mL of water and dried over MgSO4. After filtration of the MgSO4, the volatiles were evaporated under reduced pressure. The residue was purified by atmospheric distillation to give the product as a colorless oil dimethyl(hexyl)silane (10.30 g, 71.36 mmol, 82% yield). 1 H NMR (500 MHz, benzene-d6) δ 4.12 (m, 1H), δ 1.31 (m, 8H), δ 0.89 (t, 3H), δ 0.53 (m, 2H), δ 0.04 (d, 6H) Example 28 Synthesis of 1,1,3,3-tetramethyl-1-octyldisiloxane [ka]

[0100] A heat-dried 500 mL three-neck round-bottom flask was purged with a stream of argon. The flask was equipped with a dropping funnel, thermometer, condenser, and argon balloon and charged with 1,1,3,3-tetramethyldisiloxane (119.70 g, 891 mmol), Wilkinson's catalyst (5 mg, 0.0054 mmol), and 48.50 mL of anhydrous toluene. The reaction mixture was heated to 40°C, and 1-octene (20.00 g, 178.22 mmol) was added dropwise to the reaction mixture. After the addition of 1-octene, the resulting mixture was stirred at 50°C for an additional 5 hours. After this reaction time,1 Complete conversion was detected by H NMR. The reaction mixture was concentrated under reduced pressure to give the product as a colorless oil, 1,1,3,3-tetramethyl-1-octyldisiloxane (46.00 g, 186.58 mmol, 98% yield). 1 H NMR (500 MHz, CDCl3) δ 4.69 (m, 1H), δ 1.28 (m, 12H), δ 0.90 (t, 3H), δ 0.55 (m, 2H), δ 0.18 (d, 6H), δ 0.07 (s, 6H) Example 29 Synthesis of dimethyl(octyloxy)silane [ka]

[0101] A 250 mL three-neck round-bottom flask was purged with a stream of argon. The flask was equipped with a dropping funnel, a thermometer, and an argon balloon and charged with 1-octanol (5.20 g, 40.00 mmol), triethylamine (6.07 g, 60.00 mmol), and 40.0 mL of anhydrous toluene. The reaction mixture was cooled to 0 °C, and chlorodimethylsilane (4.54 g, 48.00 mmol) was added dropwise while maintaining the internal temperature between 0 °C and 5 °C. After the silane addition, the reaction was stirred overnight at room temperature. The reaction mixture was then filtered through a pad of Celite, washed with 2 × 15 mL of pentane, and the precipitated triethylamine hydrochloride was removed by filtration. The filtrate was concentrated under reduced pressure. The crude product was purified by vacuum distillation at 0.02-0.05 mbar (46°C-51°C) to give the product as a colorless oil dimethyl(octyloxy)silane (4.86 g, 25.80 mmol, 64% yield). 1 H NMR (500 MHz, benzene-d6) δ 4.88 (m, 1H), δ 3.57 (t, 2H), δ 1.54 (p, 2H), δ 1.32 (m, 2H), δ 1.23 (m, 8H), δ 0.88 (t, 3H), δ 0.15 (d, 6H) Example 30 Synthesis of ((2-hexyldecyl)oxy)dimethylsilane [ka]

[0102] A 250 mL three-neck round-bottom flask was purged with a stream of argon. The flask was equipped with a dropping funnel, a thermometer, and an argon balloon and charged with 2-hexyldecan-1-ol (6.23 g, 22.87 mmol), triethylamine (3.47 g, 34.31 mmol), and 44.2 mL of anhydrous toluene. The reaction mixture was cooled to 0 °C, and chlorodimethylsilane (2.60 g, 27.45 mmol) was added dropwise while maintaining the internal temperature between 0 °C and 5 °C. After the silane addition, the reaction was stirred overnight at room temperature. The reaction mixture was then filtered through a pad of Celite, washed with 2 × 15 mL of pentane, and the precipitated triethylamine hydrochloride was filtered off. The filtrate was concentrated under reduced pressure. The crude product was purified by vacuum distillation to give the product as a colorless oil ((2-hexyldecyl)oxy)dimethylsilane (2.61 g, 8.68 mmol, 34% yield). 1 H NMR (500 MHz, benzene-d6) δ 4.90 (p, 1H), δ 3.57 (d, 2H), δ 1.56 (m, 1H), δ 1.47 (m, 2H), δ 1.28 (m, 22H), δ 0.90 (m, 6H), δ 0.17 (d, 6H) Example 31 Synthesis of 1,1,3,3-tetramethyl-1-(octyloxy)disiloxane [ka]

[0103] A 500 mL, heat-dried, three-necked round-bottom flask was purged with a stream of argon. The flask was equipped with a dropping funnel, a thermometer, and an argon balloon and charged with 1.41 mL of BrF(Fs)2 borane catalyst solution (202 mg dissolved in 4.00 mL of anhydrous toluene) [the borane catalyst is disclosed in WO 2022 / 129966] and 1,1,3,3-tetramethyldisiloxane (128.42 g, 965 mmol). A toluene solution of 1-octanol (4.15 g, 31.87 mmol in 16 mL of anhydrous toluene) was added dropwise to the reaction mixture, and the reaction mixture was stirred at room temperature overnight. The reaction mixture was then concentrated under reduced pressure. The crude product was purified by vacuum distillation using a Vigreux column at 0.02-0.05 mbar (52-60°C) to give the product as a colorless oil, 1,1,3,3-tetramethyl-1-(octyloxy)disiloxane (8.36 g, 21.86 mmol, 69% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.04 (m, 1H), δ 3.70 (t, 2H), δ 1.60 (p, 2H), δ 1.38 (m, 2H), δ 1.27 (m, 8H), δ 0.89 (t, 3H), δ 0.21 (d, 6H), δ 0.17 (s, 6H) Example 32 Synthesis of (6-bromohexyl)dimethylsilane [ka]

[0104] A 250 mL, heat-dried, three-necked round-bottom flask was purged with a stream of argon. The flask was equipped with a thermometer, condenser, and argon balloon and charged with chlorodimethylsilane (6.38 g, 67.40 mmol), 6-bromo-1-hexene (10.00 g, 61.33 mmol), Karstedt's catalyst (69.6 μL of 2% Pt in xylene solution), and 60 mL of anhydrous tetrahydrofuran. The reaction was monitored by GC, and complete conversion was detected after overnight. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to give (6-bromohexyl)chlorodimethylsilane as a yellow oil (16.65 g, 64.61 mmol, 96% yield).

[0105] A 250 mL three-neck round-bottom flask was purged with a stream of argon. The flask was equipped with a dropping funnel, a thermometer, and an argon balloon and charged with a suspension of crushed NaBH4 (4.89 g, 129.23 mmol) in 11 mL of anhydrous tetrahydrofuran. A mixture of (6-bromohexyl)chlorodimethylsilane (16.65 g, 64.61 mmol) and 50 mL of anhydrous tetrahydrofuran was added dropwise to the suspension and stirred overnight at room temperature. The volatiles were removed under reduced pressure, and 50 mL of hexane was added to the residue. The suspension was passed through a short pad of silica gel. The filtrate was concentrated under reduced pressure. The residue was further purified by vacuum distillation at 0.02–0.05 mbar (38–39 °C) to give the product as a colorless oil, (6-bromohexyl)dimethylsilane (9.70 g, 43.45 mmol, 67% yield). 1 H NMR (500 MHz, benzene-d6) δ 4.09 (m, 1H), δ 2.95 (t, 2H), δ 1.48 (p, 2H), δ 1.20-1.04 (m, 6H), δ 0.48-0.4 (m, 2H) δ 0.02 (d, 6H) Example 33 Synthesis of ((6-bromohexyl)oxy)dimethylsilane [ka]

[0106] A 250 mL three-neck round-bottom flask was purged with a stream of argon. The flask was equipped with a dropping funnel, a thermometer, and an argon balloon and charged with 6-bromo-1-hexanol (8.00 g, 44.20 mmol), triethylamine (6.70 g, 66.30 mmol), and 44.2 mL of anhydrous toluene. The reaction mixture was cooled to 0 °C, and chlorodimethylsilane (5.02 g, 53.04 mmol) was added dropwise while maintaining the internal temperature between 0 °C and 5 °C. After the silane addition, the reaction was stirred overnight at room temperature. The reaction mixture was then filtered through a pad of Celite, washed with 2 × 15 mL of pentane, and the precipitated triethylamine hydrochloride was removed by filtration. The filtrate was concentrated under reduced pressure. The crude product was purified by vacuum distillation at 0.02-0.05 mbar (63-64°C) to give the product as a colorless oil ((6-bromohexyl)oxy)dimethylsilane (7.27 g, 30.39 mmol, 63% yield). 1 H NMR (500 MHz, benzene-d6) δ 4.85 (m, 1H), δ 3.47 (t, 2H), δ 2.90 (t, 2H), δ 1.45 (m, 2H), δ 1.37 (m, 2H), δ 1.11 (m, 4H) δ 0.14 (d, 6H) Example 34 Synthesis of ((5-bromopentyl)oxy)dimethylsilane [ka]

[0107] Triethylamine (8.39 g, 82.94 mmol, 1.50 equiv.) was added to a stirred mixture of 5-bromopentan-1-ol (9.24 g, 55.29 mmol, 1.00 equiv.) and 50 ml of dry toluene under an Ar atmosphere. Chlorodimethylsilane (6.28 g, 66.35 mmol, 1.20 equiv.) was added, and the mixture became a white slurry. This was shaken several times and then left stirring overnight. After 16 h, the mixture was filtered (glass frit), and the precipitate was rinsed with toluene. The filtrate was evaporated. The residue was diluted with petroleum ether (approximately 20 mL) to give a white precipitate, which was isolated by centrifugation. The clear solution was concentrated. The residual oil was purified by vacuum distillation at 1 mbar to give the product as a colorless oil: ((5-bromopentyl)oxy)dimethylsilane (9.23 g, 40.99 mmol, 74% yield). 1 H NMR (500 MHz, benzene-d6) δ 4.84 (m, 1H), δ 3.42 (t, 2H), δ 2.92 (t, 2H), δ 1.50-1.43 (m, 2H), δ 1.35-1.18 (m, 4H), δ 0.13 (d, 6H) Example 35 Synthesis of ((4-bromobutyl)oxy)dimethylsilane [ka]

[0108] Triethylamine (7.93 g, 78.42 mmol, 1.50 equiv.) was added to a stirred mixture of 4-bromobutan-1-ol (8.00 g, 52.28 mmol, 1.00 equiv.) and 50 mL of dry toluene under an Ar atmosphere. Chlorodimethylsilane (5.93 g, 62.74 mmol, 1.20 equiv.) was added, and the mixture became a white slurry. This was shaken several times and then left stirring overnight. After 16 h, the mixture was filtered (glass frit), and the precipitate was rinsed with toluene. The filtrate was evaporated. The residue was diluted with petroleum ether (approximately 20 mL) to give a white precipitate, which was isolated by centrifugation. The clear solution was concentrated. The residual oil was purified by vacuum distillation at 10 mbar (65-70° C.) to give the product as a colorless oil ((4-bromobutyl)oxy)dimethylsilane (7.65 g, 36.22 mmol, 69% yield). 1 H NMR (500 MHz, benzene-d6) δ 4.78 (m, 1H), δ 3.36 (t, 2H), δ 2.96 (t, 2H), δ 1.68-1.56 (m, 2H), δ 1.46-1.34 (m, 2H), δ 0.10 (d, 6H) Example 36 Synthesis of 1-(4-bromobutoxy)-1,1,3,3-tetramethyldisiloxane [ka]

[0109] A 250 mL, three-necked, heat-dried round-bottom flask was purged with a stream of argon. The flask was equipped with a dropping funnel, a thermometer, and an argon balloon and charged with 100 μL of BrF(Fs)2 borane catalyst solution (58.42 mg dissolved in 100 μL) [the borane catalyst is disclosed in WO 2022 / 129966] and 1,1,3,3-tetramethyldisiloxane (105.34 g, 784.22 mmol, 30 equiv.). A toluene solution of 4-bromo-1-butanol (4.00 g, 26.14 mmol in 16 mL of anhydrous toluene) was added dropwise to the reaction mixture, and the reaction mixture was stirred at room temperature overnight. The reaction mixture was then concentrated under reduced pressure. The crude product was purified by vacuum distillation using a Vigreux column at 5 mbar (65°C-75°C) to give the product as a colorless oil, 1-(4-bromobutoxy)-1,1,3,3-tetramethyldisiloxane (4.56 g, 15.98 mmol, 61% yield). 1 H NMR (500 MHz, benzene-d6) δ 4.99 (m, 1H), δ 3.49 (t, 2H), δ 3.00 (t, 2H), δ 1.74.1.61 (m, 2H), δ 1.54-1.40 (m, 2H), δ 0.18 (d, 6H), δ 0.10 (s, 6H) Synthesis of mixed silyl acetals (general procedures E-F)

[0110] BrF(F3s)2 and BrF(F4)2 borane catalysts (defined in each example) as disclosed in WO 2022 / 129966 were applied in the synthesis.

[0111] General Procedure E A heated, three-necked round-bottom flask was purged with a stream of argon. The flask was equipped with a septum, thermometer, and argon balloon and filled with a mixture of anhydrous toluene (1.0 mL toluene / 1.0 mmol ester) and the ester. The catalyst solution was added to the reaction mixture in one portion, followed by the dropwise addition of the silane, maintaining the internal temperature between 20 and 30 °C. The reaction mixture was stirred at room temperature (as specified in the examples) for several hours. The reaction was monitored by TLC (hexane / ethyl acetate 9 / 1, PMA visualization; if different, as specified in the examples). After completion of the reaction, 1 mL of EtOAc, 0.6 mL of MeCN, and silica gel were added to the reaction mixture, stirred for an additional 10 minutes, and the silica gel was filtered off and washed with 2 × 25 mL of n-pentane. The volatiles were removed under reduced pressure to give the crude product, which was purified by flash column chromatography or simple filtration through a short pad of silica to give the product.

[0112] General Procedure F A heated, dried, three-necked round-bottom flask was purged with a stream of argon. The flask was equipped with a septum, a thermometer, and an argon balloon and charged with the catalyst and anhydrous toluene (4.00 ml). The mixture of ester and silane was added dropwise to the catalyst solution, maintaining the internal temperature at 20-30°C. The reaction mixture was stirred for 12 hours. 1 The reaction was monitored by H NMR or TLC (specified in the examples). After completion of the reaction, 1 ml of EtOAc, 0.6 ml of MeCN, and silica gel were added to the reaction mixture, stirred for an additional 10 min, and the silica gel was filtered off and washed with 2 x 15 ml of n-pentane. The volatiles were removed under reduced pressure to give the crude product, which was purified by flash column chromatography or simple filtration through a short pad of silica to give the product. Example of mixed silyl acetal synthesis Example 37 Synthesis of ((6-bromo-1-(octyloxy)hexyl)oxy)dimethyl(octyl)silane [ka]

[0113] ((6-Bromo-1-(octyloxy)hexyl)oxy)dimethyl(octyl)silane was prepared from octyl 6-bromohexanoate (4.00 g, 13.02 mmol) and dimethyl(octyl)silane (1.1 equiv., 2.47 g, 14.32 mmol) using 616 μl of BrF(Fs)2 borane catalyst solution (189 mg of catalyst dissolved in 4.00 ml of anhydrous toluene) according to general procedure E. The reaction was complete after 2 h. The crude product was purified by flash column chromatography with gradient elution (0–10% EtOAc in n-hexane) to give ((6-bromo-1-(octyloxy)hexyl)oxy)dimethyl(octyl)silane (4.72 g, 9.84 mmol, 76% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 4.79 (dt, 1H), δ3.73-3.69 (dq, 1H), δ 3.35-3.31 (dq, 1H), δ 2.95 (t, 2H), δ1.71-1.57 (m, 4H), δ 1.47-1.19 (m, 28H), δ 0.92-0.87 (t, 6H), δ 0.71 (dd, 2H), δ 0.2 (d, 6H) Example 38 Synthesis of ((1-((6-bromohexyl)oxy)octyl)oxy)dimethyl(octyl)silane [ka]

[0114] ((1-((6-Bromohexyl)oxy)octyl)oxy)dimethyl(octyl)silane was prepared from 6-bromohexyl octanoate (5.00 g, 16.27 mmol) and dimethyl(octyl)silane (1.1 equiv., 3.09 g, 17.90 mmol) using 770 μl of BrF(Fs)2 borane catalyst solution (189 mg dissolved in 4.00 ml of anhydrous toluene) according to general procedure E. The reaction was complete after 2 h. The crude product was purified by flash column chromatography with gradient elution (0–10% EtOAc in n-hexane) to give ((1-((6-bromohexyl)oxy)octyl)oxy)dimethyl(octyl)silane (4.26 g, 8.88 mmol, 55% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 4.84 (t, 1H), δ3.68-3.64 (dq, 1H), δ 3.30-3.27 (dq, 1H), δ 2.94 (t, 2H), δ1.84-1.77 (m, 1H), δ 1.75-1.68 (m, 1H), δ 1.54-1.44 (m, 8H), δ 1.39 (m, 2H), δ1.36-1.17 (m, 20H), δ 0.92-0.87 (t, 6H), δ 0.71 (dd, 2H), δ 0.22 (d, 6H) Example 39 Synthesis of ((6-bromo-1-(decyloxy)hexyl)oxy)(hexyl)dimethylsilane [ka]

[0115] ((6-Bromo-1-(decyloxy)hexyl)oxy)(hexyl)dimethylsilane was prepared from decyl 6-bromohexanoate (4.00 g, 11.93 mmol) and dimethyl(hexyl)silane (1.1 equiv., 1.89 g, 13.12 mmol) using 573 μl of BrF(Fs)2 borane catalyst solution (186 mg of catalyst dissolved in 4.00 ml of anhydrous toluene) according to general procedure E. The reaction was complete after 2 h. The crude product was purified by flash column chromatography with gradient elution (0–10% EtOAc in n-hexane) to give ((6-bromo-1-(decyloxy)hexyl)oxy)(hexyl)dimethylsilane (4.52 g, 9.42 mmol, 79% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 4.78 (t, 1H), δ3.73-3.69 (dq, 1H), δ 3.36-3.31 (dq, 1H), δ 2.94 (t, 2H), δ1.71-1.56 (m, 4H), δ 1.54-1.47 (m, 2H), δ 1.46-1.38 (m, 4H), δ1.37-1.17 (m, 22H), δ 0.93-0.88 (t, 6H), δ 0.69 (dd, 2H), δ 0.21 (d, 6H) Example 40 Synthesis of ((10-bromo-1-(octyloxy)decyl)oxy)(hexyl)dimethylsilane [ka]

[0116] ((10-Bromo-1-(octyloxy)decyl)oxy)(hexyl)dimethylsilane was prepared from octyl 10-bromodecanoate (5.00 g, 11.69 mmol) and dimethyl(hexyl)silane (1.1 equiv., 1.86 g, 12.86 mmol) using 517 μl of BrF(Fs)2 borane catalyst solution (202 mg dissolved in 4.00 ml of anhydrous toluene) according to general procedure E. The reaction was complete after overnight. The crude product was purified by flash column chromatography with gradient elution (0–10% EtOAc in n-hexane) to give ((10-bromo-1-(octyloxy)decyl)oxy)(hexyl)dimethylsilane (3.60 g, 7.10 mmol, 61% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 4.87 (t, 1H), δ3.77-3.72 (dq, 1H), δ 3.39-3.35 (dq, 1H), δ 2.95 (t, 2H), δ1.86-1.78 (m, 1H), δ 1.77-1.70 (m, 1H), δ 1.67-1.61 (p, 2H), δ 1.56-1.20 (m, 26H), δ1.17-1.11 (p, 4H), δ 1.10-1.01 (m, 2H), δ 0.94-0.86 (m, 6H), δ 0.71 (dd, 2H), δ 0.23 (d, 6H) Example 41 Synthesis of ((1-((6-bromohexyl)oxy)decyl)oxy)(hexyl)dimethylsilane [ka]

[0117] ((1-((6-Bromohexyl)oxy)decyl)oxy)(hexyl)dimethylsilane was prepared from 6-bromohexyldecanoate (5.00 g, 14.91 mmol) and dimethyl(hexyl)silane (1.1 equiv., 2.37 g, 16.40 mmol) using 717 μl of BrF(Fs)2 borane catalyst solution (186 mg dissolved in 4.00 ml of anhydrous toluene) according to general procedure E. The reaction was complete after 3 h. The crude product was purified by flash column chromatography with gradient elution (0 to 10% EtOAc in n-hexane) to give ((1-((6-bromohexyl)oxy)decyl)oxy)(hexyl)dimethylsilane (5.04 g, 10.51 mmol, 71% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 4.84 (t, 1H), δ3.68-3.64 (dq, 1H), δ 3.30-3.26 (dq, 1H), δ 2.94 (t, 2H), δ1.85-1.77 (m, 1H), δ 1.76-1.68 (m, 1H), δ 1.61-1.41 (m, 8H), δ1.40-1.15 (m, 22H), δ 0.92-0.88 (m, 6H), δ 0.70 (dd, 2H), δ 0.23 (d, 6H). Example 42 Synthesis of ((1-((9-bromononyl)oxy)octyl)oxy)(hexyl)dimethylsilane [ka]

[0118] ((1-((9-bromononyl)oxy)octyl)oxy)(hexyl)dimethylsilane was prepared from 9-bromononyl octanoate (5.00 g, 14.31 mmol) and dimethyl(hexyl)silane (1.1 equiv., 2.27 g, 15.74 mmol) using 633 μl of BrF(Fs)2 borane catalyst solution (202 mg dissolved in 4.00 ml of anhydrous toluene) according to general procedure E. The reaction was complete after stirring overnight. The crude product was purified by flash column chromatography with gradient elution (0–10% EtOAc in n-hexane) to give ((1-((9-bromononyl)oxy)octyl)oxy)(hexyl)dimethylsilane (6.00 g, 12.15 mmol, 85% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 4.87 (t, 1H), δ3.77-3.72 (dq, 1H), δ 3.39-3.35 (dq, 1H), δ 2.95 (t, 2H), δ1.86-1.78 (m, 1H), δ 1.77-1.68 (m, 1H), δ 1.66-1.58 (m, 2H), δ1.57-1.18 (m, 24H), δ 1.17-1.10 (m, 4H) δ 1.09-1.01 (m, 2H), δ0.92-0.86 (m, 6H), δ 0.71 (dd, 2H), δ 0.23 (d, 6H) Example 43 Synthesis of 12-(5-bromopentyl)-10,10-dimethyl-9,11,13-trioxa-10-silahenicosane [ka]

[0119] 12-(5-Bromopentyl)-10,10-dimethyl-9,11,13-trioxa-10-silahenicosane was prepared from octyl 6-bromohexanoate (5.00 g, 16.27 mmol) and dimethyl(octyloxy)silane (1.1 equiv., 3.37 g, 17.90 mmol) using 503 μl of BrF(Fs)2 borane catalyst solution (253 mg dissolved in 3.50 ml of anhydrous toluene) according to General Procedure E. The reaction was complete after stirring overnight. The crude product was purified by flash column chromatography with gradient elution (0–10% EtOAc in n-hexane) to give 12-(5-bromopentyl)-10,10-dimethyl-9,11,13-trioxa-10-silahenicosane (3.78 g, 7.63 mmol, 47% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 4.93 (t, 1H), δ3.85-3.83 (dq, 1H), δ 3.76-3.73 (t, 2H), δ 3.40-3.39 (dq, 1H), 2.97 (t, 2H), δ 1.80-1.60 (m, 6H), δ 1.60-1.50 (m, 2H), δ1.50-1.30 (m, 6H), δ 1.57-1.18 (m, 18H), δ 0.92-0.89 (m, 6H), δ 0.23 (d, 6H) Example 44 Synthesis of 1-bromo-8-heptyl-10,10-dimethyl-7,9,11-trioxa-10-silanonadecane [ka]

[0120] 1-Bromo-8-heptyl-10,10-dimethyl-7,9,11-trioxa-10-silanonadecane was prepared from 6-bromohexyl octanoate (5.00 g, 16.27 mmol) and dimethyl(octyloxy)silane (1.1 equiv., 3.37 g, 17.90 mmol) using 706 μL of BrF(Fs)2 borane catalyst solution (206 mg dissolved in 4.00 mL of anhydrous toluene) according to general procedure E. The reaction was complete after stirring overnight. The crude product was purified by flash column chromatography with gradient elution (0–10% EtOAc in n-hexane) to give 1-bromo-8-heptyl-10,10-dimethyl-7,9,11-trioxa-10-silanonadecane (5.00 g, 10.08 mmol, 62% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 4.96 (t, 1H), δ3.79-3.71 (dq, 3H), δ 3.34-3.30 (dq, 1H), δ 2.94 (t, 2H), δ1.92-1.75 (m, 2H), δ 1.65-1.11 (m, 30H), δ 0.90-0.87 (m, 6H), δ 0.25 (d, 6H)

[0121] Example 45 Synthesis of 1-((6-bromo-1-(octyloxy)hexyl)oxy)-1,1,3,3-tetramethyl-3-octyldisiloxane [ka] 1-((6-Bromo-1-(octyloxy)hexyl)oxy)-1,1,3,3-tetramethyl-3-octyldisiloxane was prepared from octyl 6-bromohexanoate (5.0 g, 16.27 mmol) and 1,1,3,3-tetramethyl-1-octyldisiloxane (1.1 equivalents, 4.41 g, 17.90 mmol) using 782 μL of BrF(Fs)2 borane catalyst solution (186 mg dissolved in 4.00 mL of anhydrous toluene) according to General Procedure E. The reaction was complete after 3 hours. The crude product was purified by flash column chromatography with gradient elution (0–10% EtOAc in n-hexane) to give 1-((6-bromo-1-(octyloxy)hexyl)oxy)-1,1,3,3-tetramethyl-3-octyldisiloxane (7.80 g, 14.08 mmol, 87% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 4.92 (dt, 1H), δ3.85-3.80 (dq, 1H), δ 3.40-3.36 (dq, 1H), δ 2.96 (t, 2H), δ1.79-1.61 (m, 4H), δ 1.56-1.50 (p, 2H), δ 1.48-1.20 (p, 26H), δ0.92-0.87 (m, 6H), δ 0.66 (m, 2H), δ 0.23 (d, 6H), δ 0.19 (s, 6H). Example 46 Synthesis of 1-((1-((6-bromohexyl)oxy)octyl)oxy)-1,1,3,3-tetramethyl-3-octyldisiloxane [ka]

[0122] 1-((1-((6-Bromohexyl)oxy)octyl)oxy)-1,1,3,3-tetramethyl-3-octyldisiloxane was prepared from 6-bromohexyl octanoate (5.0 g, 16.27 mmol) and 1,1,3,3-tetramethyl-1-octyldisiloxane (1.1 equivalents, 4.41 g, 17.90 mmol) using 589 μl of BrF(Fs)2 borane catalyst solution (216 mg dissolved in 3.50 ml of anhydrous toluene) according to General Procedure E. The reaction was complete after stirring overnight. The crude product was purified by flash column chromatography with gradient elution (0–10% EtOAc in n-hexane) to give 1-((1-((6-bromohexyl)oxy)octyl)oxy)-1,1,3,3-tetramethyl-3-octyldisiloxane (6.92 g, 12.49 mmol, 77% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 4.97 (t, 1H), δ3.79-3.75 (dq, 1H), δ 3.35-3.30 (dq, 1H), δ 2.94 (t, 2H), δ1.92-1.75 (m, 2H), δ 1.60-1.13 (m, 30H), δ 0.92-0.87 (m, 6H), δ 0.66 (m, 2H), δ 0.22 (d, 6H), δ 0.19 (s, 6H) Example 47 Synthesis of 1-((6-bromo-1-(octyloxy)hexyl)oxy)-1,1,3,3-tetramethyl-3-(octyloxy)disiloxane [ka]

[0123] 1-((6-Bromo-1-(octyloxy)hexyl)oxy)-1,1,3,3-tetramethyl-3-(octyloxy)disiloxane was prepared from octyl 6-bromohexanoate (5.0 g, 16.27 mmol) and 1,1,3,3-tetramethyl-1-(octyloxy)disiloxane (1.1 equivalents, 4.70 g, 17.90 mmol) using 144 μL of BrF(Fs)2 borane catalyst solution (202 mg dissolved in 4.00 mL of anhydrous toluene) according to General Procedure E. The reaction was complete after stirring overnight. The crude product was purified by flash column chromatography with gradient elution (0–10% EtOAc in n-hexane) to give 1-((6-bromo-1-(octyloxy)hexyl)oxy)-1,1,3,3-tetramethyl-3-(octyloxy)disiloxane (8.29 g, 14.55 mmol, 89% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 4.95 (dt, 1H), δ3.86-3.82 (dq, 1H), δ 3.76-3.72 (t, 2H), δ 3.41-3.37 (dq, 1H), δ 2.96 (t, 2H), δ 1.82-1.59 (m, 6H), δ 1.56-1.51 (p, 2H), δ 1.46-1.35 (m, 6H), δ1.34-1.18 (m, 18H), δ 0.90-0.87 (m, 6H), δ 0.27 (d, 6H), δ 0.21 (s, 6H). Example 48 Synthesis of 1-((1-((6-bromohexyl)oxy)octyl)oxy)-1,1,3,3-tetramethyl-3-(octyloxy)disiloxane [ka]

[0124] 1-((1-((6-Bromohexyl)oxy)octyl)oxy)-1,1,3,3-tetramethyl-3-(octyloxy)disiloxane was prepared from 6-bromohexyl octanoate (4.00 g, 13.01 mmol) and 1,1,3,3-tetramethyl-1-(octyloxy)disiloxane (1.1 equivalents, 3.76 g, 14.32 mmol) using 565 μL of BrF(Fs)2 borane catalyst solution (206 mg dissolved in 4.00 mL of anhydrous toluene) according to General Procedure E. The reaction was complete after stirring overnight. The crude product was purified by flash column chromatography with gradient elution (0–10% EtOAc in n-hexane) to give 1-((1-((6-bromohexyl)oxy)octyl)oxy)-1,1,3,3-tetramethyl-3-(octyloxy)disiloxane (4.02 g, 7.05 mmol, 54% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 5.00 (dt, 1H), δ3.82-3.71 (m, 3H), δ 3.36-3.31 (dq 1H), δ 2.94 (t, 2H), δ1.95-1.76 (m, 2H), δ 1.68-1.45 (m, 8H), δ 1.45-1.11 (m, 22H), δ0.90-0.87 (m, 6H), δ 0.29 (d, 6H), δ 0.22 (s, 6H) Example 49 Synthesis of (6-bromohexyl)dimethyl((1-(octyloxy)octyl)oxy)silane [ka]

[0125] (6-Bromohexyl)dimethyl((1-(octyloxy)octyl)oxy)silane was prepared from octyl octanoate (5.00 g, 19.50 mmol) and (6-bromohexyl)dimethylsilane (1.1 equiv., 4.79 g, 21.45 mmol) using 603 μl of BrF(Fs)2 borane catalyst solution (248 mg dissolved in 3.43 ml of anhydrous toluene) according to general procedure E. The reaction was complete after stirring overnight. The crude product was purified by flash column chromatography with gradient elution (0–5% EtOAc in n-hexane) to give (6-bromohexyl)dimethyl((1-(octyloxy)octyl)oxy)silane (9.11 g, 18.99 mmol, 97% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 4.87 (dt, 1H), δ3.77-3.72 (dq, 1H), δ 3.40-3.35 (dq 1H), δ 2.99 (t, 2H), δ1.87-1.80 (m, 1H), δ 1.77-1.70 (m, 1H), δ 1.68-1.63 (m, 2H), δ1.57-1.49 (p, 4H), δ 1.48-1.40 (p, 2H), δ 1.39-1.14 (m, 22H), δ0.92-0.88 (m, 6H), δ 0.65 (m, 2H), δ 0.23 (d, 6H). Example 50 Synthesis of 1-bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silanonadecane [ka]

[0126] 1-Bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silanonadecane was prepared from octyl octanoate (5.00 g, 19.50 mmol) and ((6-bromohexyl)oxy)dimethylsilane (1.1 equiv., 5.13 g, 21.45 mmol) using 603 μL of BrF(Fs)2 borane catalyst solution (253 mg dissolved in 3.50 mL of anhydrous toluene) according to general procedure E. The reaction was complete after stirring overnight. The crude product was purified by flash column chromatography with gradient elution (0–5% EtOAc in n-hexane) to give 1-bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silanonadecane (8.20 g, 16.54 mmol, 85% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 4.99 (dt, 1H), δ3.86-3.84 (dq, 1H), δ 3.70-3.67 (t, 2H), δ 3.42-3.41 (dq 1H), δ 2.96 (t, 2H), δ 1.87-1.81 (m, 1H), δ 1.79-1.70 (m, 1H), δ 1.70-1.64 (m, 2H), δ1.62-1.40 (m, 8H), δ 1.40-1.13 (m, 20H), δ 0.91-0.89 (m, 6H), δ 0.27 (d, 6H) Example 51 Synthesis of 10-(5-bromopentyl)-15-hexyl-12,12-dimethyl-9,11,13-trioxa-12-silatricosane [ka]

[0127] 10-(5-Bromopentyl)-15-hexyl-12,12-dimethyl-9,11,13-trioxa-12-silatricosane was prepared from octyl 6-bromohexanoate (5.00 g, 16.27 mmol) and ((2-hexyldecyl)oxy)dimethylsilane (1.1 equivalents, 5.38 g, 17.90 mmol) using 503 μl of BrF(Fs)2 borane catalyst solution (253 mg dissolved in 3.50 ml of anhydrous toluene) according to General Procedure E. The reaction was complete after stirring overnight. The crude product was purified by flash column chromatography with gradient elution (0–2% EtOAc in n-hexane) to give 10-(5-bromopentyl)-15-hexyl-12,12-dimethyl-9,11,13-trioxa-12-silatricosane (6.66 g, 10.96 mmol, 67% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 4.93 (dt, 1H), δ3.86-3.82 (dq, 1H), δ 3.72-3.71 (d, 2H), δ 3.42-3.37 (dq 1H), δ 2.96 (t, 2H), δ 1.81-1.47 (m, 9H), δ 1.47-1.18 (m, 36H), δ 0.91-0.88 (m, 9H), δ 0.26 (d, 6H) Example 52 Synthesis of 1-bromo-8-heptyl-13-hexyl-10,10-dimethyl-7,9,11-trioxa-10-silahenicosane [ka]

[0128] 1-Bromo-8-heptyl-13-hexyl-10,10-dimethyl-7,9,11-trioxa-10-silahenicosane was prepared from 6-bromohexyl octanoate (4.00 g, 13.01 mmol) and ((2-hexyldecyl)oxy)dimethylsilane (1.1 equivalents, 4.30 g, 14.32 mmol) using 402 μl of BrF(Fs)2 borane catalyst solution (253 mg dissolved in 3.50 ml of anhydrous toluene) according to General Procedure E. The reaction was complete after stirring overnight. The crude product was purified by flash column chromatography with gradient elution (0–2% EtOAc in n-hexane) to give 1-bromo-8-heptyl-13-hexyl-10,10-dimethyl-7,9,11-trioxa-10-silahenicosane (4.03 g, 6.63 mmol, 51% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 4.99 (dt, 1H), δ3.82-3.78 (dq, 1H), 3.74-3.73 (d, 2H), 3.37-3.33 (dq 1H), 2.96 (t, 2H), δ1.88-1.75 (m, 2H), δ 1.75-1.45 (m, 9H), δ 1.45-1.14 (m, 34H), δ0.92-0.89 (m, 9H), δ 0.28 (d, 6H) Example 53 Synthesis of triethyl(((9Z,12Z)-1-methoxyoctadeca-9,12-dien-1-yl)oxy)silane [ka]

[0129] Triethyl(((9Z,12Z)-1-methoxyoctadeca-9,12-dien-1-yl)oxy)silane was prepared from methyl (9Z,12Z)-octadeca-9,12-dienoate (12.68 g, 43.07 mmol) and triethylsilane (5.16 g, 44.36 mmol) using 208 mg (0.43 mmol) of BrF(F) borane catalyst according to general procedure F. 1The reaction was monitored by H NMR. After purification, the product was obtained as a yellowish oil, triethyl(((9Z,12Z)-1-methoxyoctadeca-9,12-dien-1-yl)oxy)silane (14.61 g, 35.56 mmol, 83% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.50-5.42 (m, 4H), δ 4.74 (t, 1H), δ 3.21 (s, 3H), δ 2.86 (t, 2H), δ 2.10-2.02 (m, 4H), δ1.77-1.68 (m, 1H), δ 1.68-1.58 (m, 1H), δ 1.58-1.50 (m, 1H), δ1.50-1.40 (m, 1H), δ 1.40-1.20 (m, 14H), δ 1.03-0.99 (t, 9H), δ0.90-0.80 (m, 3H), δ 0.67-0.62 (q, 6H) Example 54 Synthesis of triethyl(((9Z,12Z,15Z)-1-methoxyoctadeca-9,12,15-trien-1-yl)oxy)silane [ka]

[0130] Triethyl(((9Z,12Z,15Z)-1-methoxyoctadeca-9,12,15-trien-1-yl)oxy)silane was prepared from methyl (9Z,12Z,15Z)-octadeca-9,12,15-trienoate (11.55 g, 39.50 mmol) and triethylsilane (4.73 g, 40.68 mmol) using 191 mg (0.39 mmol) of BrF(F) borane catalyst according to general procedure F. The reaction mixture was stirred overnight at 30 °C. The reaction was monitored by TLC (hexane / ethyl acetate 9:1). After purification, the product was obtained as a yellowish oil, triethyl(((9Z,12Z,15Z)-1-methoxyoctadeca-9,12,15-trien-1-yl)oxy)silane (15.81 g, 38.68 mmol, 98% yield). 1H NMR (500 MHz, benzene-d6) δ 5.32-5.17 (m, 6H), δ 4.56 (t, 1H), δ 3.02 (s, 3H), δ 2.72-2.60 (m, 4H), δ 1.93-1.75 (m, 4H), δ1.64-1.39 (m, 2H), δ 1.36-1.22 (m, 2H), δ 1.16-1.01 (m, 8H), δ 0.84 (t, 9H), δ 0.72 (m, 3H), δ 0.50-0.42 (q, 6H) Example 55 Synthesis of (((5Z,8Z,11Z,14Z,17Z)-1-ethoxyicosa-5,8,11,14,17-pentaen-1-yl)oxy)triethylsilane [ka]

[0131] (((5Z,8Z,11Z,14Z,17Z)-1-ethoxyicosa-5,8,11,14,17-pentaen-1-yl)oxy)triethylsilane was prepared from ethyl (5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaenoate (13.28 g, 40.17 mmol) and triethylsilane (4.81 g, 41.37 mmol) using 194 mg (0.40 mmol) of BrF(F) borane catalyst according to general procedure F. 1 The reaction was monitored by H NMR. The product was obtained as a yellowish oil (((5Z,8Z,11Z,14Z,17Z)-1-ethoxyicosa-5,8,11,14,17-pentaen-1-yl)oxy)triethylsilane (17.01 g, 38.08 mmol, 95% yield). 1H NMR (500 MHz, benzene-d6) δ 5.52-5.39 (m, 10H), δ 4.82 (t, 1H), δ 3.70-3.64 (dp, 1H), δ 3.37-3.31 (dp, 1H), δ 2.91-2.80 (m, 8H), δ2.16-2.07 (m, 2H), δ 2.07-1.98 (m, 2H), δ 1.83-1.74 (m, 1H), δ1.74-1.65 (m, 1H), δ 1.65-1.54 (m, 2H), δ 1.15 (t, 3H), δ 1.04 (t, 9H), δ 0.92 (t, 3H), δ 0.67 (q, 6H) Example 56 Synthesis of triethyl(((4R)-1-methoxy-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentyl)oxy)silane [ka]

[0132] Triethyl(((4R)-1-methoxy-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentyl)oxy)silane was prepared from methyl (4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentanoate (1.82 g, 4.50 mmol) and triethylsilane (0.57 g, 4.95 mmol) using 21.72 mg (0.045 mmol) of BrF(F) borane catalyst according to general procedure F. The reaction was monitored by TLC (hexane / ethyl acetate 9:1, PMA visualization). The crude product was purified by flash column chromatography with gradient elution (0–10% EtOAc in n-hexane) to give triethyl(((4R)-1-methoxy-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentyl)oxy)silane (0.84 g, 1.61 mmol, 36% yield) as a white solid. 1 H NMR (500 MHz, benzene-d6) δ 4.81-476 (m, 1H), δ4.76-4.68 (m, 1H), δ 3.41 (s, 3H), δ 3.25 (d, 3H), δ1.95-1.10 (m, 25H), δ 1.10-1.02 (t, 12H), δ 1.00 (d, 3H), δ 0.75 (s, 3H), δ 0.71-0.66 (dq, 6H), δ 0.57 (s, 3H) Example 57 Synthesis of 6-methoxy-6-((triethylsilyl)oxy)hexyl 2-(decylthio)hexanoate [ka]

[0133] 6-Methoxy-6-((triethylsilyl)oxy)hexyl 2-(decylthio)hexanoate was prepared from 6-methoxy-6-oxohexyl 2-(decylthio)hexanoate (10.1 g, 24.24 mmol) and triethylsilane (3.10 g, 26.66 mmol) using 117 mg (0.24 mmol) of BrF(F) borane catalyst according to general procedure F. The reaction was monitored by TLC (hexane / ethyl acetate 9:1, PMA visualization). The crude product was purified by flash column chromatography with gradient elution (0–10% EtOAc in n-hexane) to give 6-methoxy-6-((triethylsilyl)oxy)hexyl 2-(decylthio)hexanoate (4.35 g, 8.16 mmol, 34% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 4.69 (t, 1H), δ4.12-4.03 (m, 2H), δ 3.29 (dt, 1H), δ 3.19 (s, 3H) δ3.75-3.65 (m, 1H), δ 3.65-3.57 (m, 1H), δ 2.06-1.95 (m, 1H), δ1.79-1.77 (m, 1H), δ 1.77-1.63 (m, 1H), δ 1.62-1.54 (m, 3H), δ1.53-1.46 (m, 2H), δ 1.43-1.14 (m, 22H), δ 1.02 (t, 9H), δ δ 0.90 (t, 3H), δ 0.80 (t, 3H), δ 0.64 (q, 6H) Example 58 Synthesis of 6-methoxy-6-((triethylsilyl)oxy)hexyl 2-(pentylthio)decanoate [ka]

[0134] 6-Methoxy-6-((triethylsilyl)oxy)hexyl 2-(pentylthio)decanoate was prepared from 6-methoxy-6-oxohexyl 2-(pentylthio)decanoate (9.00 g, 22.35 mmol) and triethylsilane (2.86 g, 24.59 mmol) using 108 mg (0.22 mmol) of BrF(F)2 borane catalyst according to general procedure F. The reaction mixture was stirred overnight at room temperature. The reaction was monitored by TLC (hexane / ethyl acetate 9:1, PMA visualization). The crude product was purified by flash column chromatography with gradient elution (0–1% EtOAc in n-hexane) to give 6-methoxy-6-((triethylsilyl)oxy)hexyl 2-(pentylthio)decanoate (5.79 g, 11.16 mmol, 50% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 4.69 (t, 1H), δ4.14-4.03 (m, 2H), δ 3.31(dt, 1H), δ 3.19 (s, 3H) δ3.73-3.64 (m, 1H), δ 3.62-3.53 (m, 1H), δ 2.09-1.98 (m, 1H), δ1.84-1.72 (m, 1H), δ 1.70-1.62 (m, 1H), δ 1.62-1.46 (m, 5H), δ1.46-1.33 (m, 4H), δ 1.31-1.12 (m, 16H), δ 1.02 (t, 9H), δ δ 0.89 (t, 3H), δ 0.81 (t, 3H), δ 0.64 (q, 6H) Example 59 Synthesis of 6-ethoxy-6-((triethylsilyl)oxy)hexyl 2-hexyldecanoate [ka]

[0135] In a dry 100 mL flask equipped with a stir bar, rubber septum, thermometer, and nitrogen inlet, 6-ethoxy-6-oxohexyl 2-hexyldecanoate (23.9 g, 60.0 mmol, 1.0 equiv.) was dissolved in anhydrous toluene (30 mL) under inert conditions (nitrogen gas). Next, a toluic solution of the catalyst BrF(F4)2 (14.49 mg in 600 μL of anhydrous toluene) was added. Finally, triethylsilane (7.47 g, 10.3 mL, 64.2 mmol, 1.07 equiv.) was added dropwise while maintaining the reaction temperature at 24–28 °C. Occasionally, hydrogen gas evolution may be observed during the initiation of the reaction, indicating the presence of a small amount of residual water in the system; however, this does not affect the outcome of the reaction. The reaction was further stirred at room temperature overnight (approximately 20 h). The reaction was monitored by TLC and NMR. After the reaction was complete, 1 ml of EtOAc, 0.6 ml of MeCN, and silica gel were added to the reaction mixture, which was stirred for an additional 10 min. The silica gel was filtered off and washed with 2 x 50 ml of n-pentane. The volatiles were removed under reduced pressure to give the product, which was used without further purification (29.00 g, 57.89 mmol, 97% yield). 1 H NMR (500 MHz, benzene-d6) δ 4.79 (t, 1H), δ 4.10 (t, 2H), δ 3.66 (m, 1H), δ 3.32 (m, 1H), δ 2.50-2.39 (m, 1H), δ1.86-1.20 (br. m, 32H), δ 1.15 (t, 3H), δ 1.04 (t, 9H), δ .91 (q, 6H), δ .67 (q, 6H), Example 60 Synthesis of 1-bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silaoctadecane [ka]

[0136] 1-Bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silaoctadecane was prepared from heptyl octanoate (727.19 mg, 3.00 mmol, 1.0 equiv) and ((6-bromohexyl)oxy)dimethylsilane (789.44 mg, 3.30 mmol, 1.1 equiv) using 100 μL of BrF(Fs)2 borane catalyst solution (1.34 mg dissolved in 100 μL of anhydrous toluene) according to general procedure E. The reaction was complete after stirring overnight. The crude product was purified by flash column chromatography with gradient elution (20% to 66% DCM in petroleum ether) to give 1-bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silaoctadecane (1.34 g, 2.86 mmol, 95% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 4.96 (m, 1H), δ3.84-3.79 (m, 1H), δ 3.66 (dt, 2H), δ 3.43-3.35 (m, 1H), δ 2.96 (t, 2H), δ 1.87-1.77 (m, 2H), δ 1.70-1.10 (br. m, 28H), δ 0.91-0.86 (m, 6H), δ 0.27 (m, 6H) Example 61 Synthesis of 1-bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silaicosane [ka]

[0137] 1-Bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silaicosane was prepared from nonyl octanoate (811.35 mg, 3.00 mmol, 1.0 equiv.) and ((6-bromohexyl)oxy)dimethylsilane (789.44 mg, 3.30 mmol, 1.1 equiv.) using 100 μL of BrF(F) borane catalyst solution (1.45 mg dissolved in 100 μL of anhydrous toluene) according to general procedure E. After stirring overnight, the reaction was complete (TLC petroleum ether:chloroform 1:1, ca. 0.4 Rf). The crude product was purified by flash column chromatography with gradient elution (20% to 66% DCM in petroleum ether) to give 1-bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silycosane (1.32 g, 2.59 mmol, 86% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 4.99 (dt, 1H), δ3.89-3.80 (m, 1H), δ 3.68 (t, 2H), δ 3.46-3.37 (m, 1H), δ 2.96 (t, 2H), δ 1.98-1.75 (m, 2H), δ 1.73-1.39 (br. m, 10H), δ 1.38-1.11 (br. m, 22H), δ 0.91 (m, 6H), δ 0.27 (d, 6H) Example 62 Synthesis of 1-bromo-10-hexyl-8,8-dimethyl-7,9,11-trioxa-8-silanonadecane [ka]

[0138] 1-Bromo-10-hexyl-8,8-dimethyl-7,9,11-trioxa-8-silanonadecane was prepared from octyl heptanoate (727.19 mg, 3.0 mmol) and ((6-bromohexyl)oxy)dimethylsilane (789.44 mg, 3.30 mmol, 1.1 equiv.) using 100 μL of BrF(Fs)2 borane catalyst solution (1.34 mg dissolved in 100 μL of anhydrous toluene) according to general procedure E. After stirring overnight, the reaction was complete (TLC petroleum ether:chloroform 1:1, ca. 0.4 Rf). The crude product was purified by flash column chromatography with gradient elution (20% to 66% DCM in petroleum ether) to give 1-bromo-10-hexyl-8,8-dimethyl-7,9,11-trioxa-8-silanonadecane (1.26 g, 2.71 mmol, 90% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 4.98 (dd, 1H), δ3.87-3.82 (m, 1H), δ 3.68 (t, 2H), δ 3.43-3.38 (m, 1H), δ 2.96 (t, 2H), δ 1.93-1.76 (m, 2H), δ 1.70-1.12 (br. m, 28H), δ 0.92-0.87 (m, 6H), δ 0.26 (d, 6H) Example 63 Synthesis of 1-bromo-8,8-dimethyl-10-octyl-7,9,11-trioxa-8-silanonadecane [ka]

[0139] 1-Bromo-8,8-dimethyl-10-octyl-7,9,11-trioxa-8-silanonadecane was prepared from octyl nonanoate (811.35 mg, 3.0 mmol) and ((6-bromohexyl)oxy)dimethylsilane (789.44 mg, 3.30 mmol, 1.1 equiv.) using 100 μL of BrF(Fs)2 borane catalyst solution (1.34 mg dissolved in 100 μL of anhydrous toluene) according to general procedure E. After stirring overnight, the reaction was complete (TLC petroleum ether:chloroform 1:1, ca. 0.4 Rf). The crude product was purified by flash column chromatography with gradient elution (20% to 66% DCM in petroleum ether) to give 1-bromo-8,8-dimethyl-10-octyl-7,9,11-trioxa-8-silanonadecane (1.29 g, 2.62 mmol, 87% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 4.99 (m, 1H), δ3.88-3.83 (m, 1H), δ 3.68 (t, 2H), δ 3.44-3.39 (m, 1H), δ 2.96 (t, 2H), δ 1.90-1.80 (m, 2H), δ 1.71-1.14 (br. m, 32H), δ 0.92-0.88 (m, 6H), δ 0.27 (d, 6H) Example 64 Synthesis of 1-bromo-8,8-dimethyl-10-nonyl-7,9,11-trioxa-8-silaheptadecane [ka]

[0140] 1-Bromo-8,8-dimethyl-10-nonyl-7,9,11-trioxa-8-silaheptadecane was prepared from hexyl decanoate (769.3 mg, 3.00 mmol, 1.0 equiv.) and ((6-bromohexyl)oxy)dimethylsilane (789.44 mg, 3.30 mmol, 1.1 equiv.) using 100 μl of BrF(F) borane catalyst solution (1.45 mg dissolved in 100 μl of anhydrous toluene) according to general procedure E. The reaction was complete after stirring overnight. The crude product was purified by flash column chromatography with gradient elution (20–65% DCM in petroleum ether) to give 1-bromo-8,8-dimethyl-10-nonyl-7,9,11-trioxa-8-silaheptadecane (1.20 g, 2.42 mmol, 81% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 4.98 (m, 1H), δ3.86-3.79 (m, 1H), δ 3.68 (t, 2H), δ 3.43-3.36 (m, 1H), δ 2.96 (t, 2H), δ 1.95-1.23 (br. m, 32H), δ 0.93-0.86 (m, 6H), δ 0.26 (d, 6H) Example 65 Synthesis of 1-bromo-8,8-dimethyl-10-pentyl-7,9,11-trioxa-8-silahenicosane [ka]

[0141] 1-Bromo-8,8-dimethyl-10-pentyl-7,9,11-trioxa-8-silahenicosane was prepared from decyl hexanoate (769.27 mg, 3.00 mmol) and ((6-bromohexyl)oxy)dimethylsilane (789.44 mg, 3.30 mmol, 1.1 equiv.) using 100 μL of BrF(F)2 borane catalyst solution (1.45 mg dissolved in 100 μL of anhydrous toluene) according to general procedure E. The reaction was complete after stirring overnight. The crude product was purified by flash column chromatography with gradient elution (20–65% DCM in petroleum ether) to afford 1-bromo-8,8-dimethyl-10-pentyl-7,9,11-trioxa-8-silahenicosane (1.04 g, 2.11 mmol, 70% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 4.98 (m, 1H), δ3.88-3.81 (m, 1H), δ 3.68 (t, 2H), δ 3.45-3.37 (m, 1H), δ 2.96 (t, 2H), δ 1.95-1.27 (br. m, 32H), δ 0.95-0.84 (m, 6H), δ 0.26 (d, 6H) Example 66 Synthesis of ((6-bromohexyl)oxy)dimethyl((oxacyclohexadecan-2-yl)oxy)silane [ka]

[0142] ((6-Bromohexyl)oxy)dimethyl((oxacyclohexadecan-2-yl)oxy)silane was prepared from oxacyclohexadecan-2-one (1.00 g, 3.827 mmol) and ((6-bromohexyl)oxy)dimethylsilane (1.00 g, 4.21 mmol, 1.1 equiv.) using 100 μL of BrF(Fs)2 borane catalyst solution (8.55 mg dissolved in 100 μL of anhydrous toluene) according to general procedure E. The reaction was complete after stirring overnight. Evaporation of the solvent gave a clear oil ((6-bromohexyl)oxy)dimethyl((oxacyclohexadecan-2-yl)oxy)silane (1.83 g, 3.83 mmol, 100% yield). 1 H NMR (500 MHz, benzene-d6) δ 4.80 (dd, 1H), δ3.85-3.78 (m, 1H), δ 3.68 (t, 2H), δ 3.40 (t, 2H), δ3.31-3.22 (m, 1H), δ 1.90-1.83 (m, 2H), δ 1.75-1.18 (br. m, 32H), δ 0.15 (d, 6H) Example 67 Synthesis of 1-(4-bromobutoxy)-1,1,3,3-tetramethyl-3-((1-(octyloxy)octyl)oxy)disiloxane [ka]

[0143] 1-(4-Bromobutoxy)-1,1,3,3-tetramethyl-3-((1-(octyloxy)octyl)oxy)disiloxane was prepared from octyl octanoate (750 mg, 2.925 mmol) and 1-(4-bromobutoxy)1,1,3,3-tetramethyldisiloxane (0.75 equiv., 625.9 mg, 2.190 mmol) using 100 μL of BrF(Fs)2 borane catalyst solution (6.54 mg dissolved in 100 μL of anhydrous toluene) according to General Procedure E. The reaction was complete after stirring overnight. The crude product was purified by flash column chromatography with gradient elution (10–90% EtOAc in petroleum ether) to give 1-(4-bromobutoxy)-1,1,3,3-tetramethyl-3-((1-(octyloxy)octyl)oxy)disiloxane (1.27 g, 2.35 mmol, 80% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 4.79 (dd, 1H), δ3.73-3.62 (m, 2H), δ 3.44 (t, 1H), δ 3.32-3.26 (m, 1H), δ1.72-1.19 (br. m, 30H), δ 0.89-0.86 (m, 6H), δ 0.15-0.08 (d, 12H) Example 68 Synthesis of 1-bromo-8,8,10-trimethyl-7,9,11-trioxa-8-silahenicosane [ka]

[0144] 1-Bromo-8,8,10-trimethyl-7,9,11-trioxa-8-silahenicosane was prepared from decyl acetate (400.03 mg, 1.997 mmol) and ((6-bromohexyl)oxy)dimethylsilane (477.73 mg, 1.997 mmol, 1.0 equiv.) using 100 μL of BrF(Fs)2 borane catalyst solution (8.93 mg dissolved in 100 μL of anhydrous toluene) according to general procedure E. The reaction was complete after stirring overnight. The crude product was purified by flash column chromatography with gradient elution (0–100% DCM and 1% TEA in petroleum ether) to afford 1-bromo-8,8,10-trimethyl-7,9,11-trioxa-8-silahenicosane (743 mg, 1.69 mmol, 85% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 5.05 (m, 1H), δ3.82-3.74 (m, 1H), δ 3.66-3.55 (m, 2H), δ 3.38-3.31 (m, 1H), δ3.01-2.92 (m, 2H), δ 1.66-1.10 (br. m, 27H), δ 0.91 (t, 3H), δ 0.20 (t, 6H) Example 69 Synthesis of 1-bromo-8,8-dimethyl-10-propyl-7,9,11-trioxa-8-silahenicosane [ka]

[0145] 1-Bromo-8,8-dimethyl-10-propyl-7,9,11-trioxa-8-silahenicosane was prepared from decyl butanoate (1.00 g, 4.028 mmol, 1.0 equiv.) and ((6-bromohexyl)oxy)dimethylsilane (1.060 g, 4.431 mmol, 1.1 equiv.) using 100 μL of BrF(Fs)2 borane catalyst solution (9.0 mg dissolved in 100 μL of anhydrous toluene) according to general procedure E. The reaction was complete after stirring overnight. The crude product was purified by flash column chromatography with gradient elution (20–65% DCM in petroleum ether) to afford 1-bromo-8,8-dimethyl-10-propyl-7,9,11-trioxa-8-silahenicosane (1.88 g, 4.0 mmol, 100% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 4.81 (dd, 1H), δ3.70-3.63 (m, 3H), δ 3.40 (t, 2H), δ 3.34-3.29 (m, 1H), δ1.90-1.83 (m, 2H), δ 1.69-1.21 (br. m, 26H), δ 0.93-0.86 (m, 6H), δ 0.16 (d, 6H) Example 70 Synthesis of 1-bromo-8,8-dimethyl-10-propyl-7,9,11-trioxa-8-silatricosane [ka]

[0146] 1-Bromo-8,8-dimethyl-10-propyl-7,9,11-trioxa-8-silatricosane was prepared from dodecyl butanoate (750 mg, 2.925 mmol, 1.0 equiv.) and ((6-bromohexyl)oxy)dimethylsilane (699.70 mg, 2.925 mmol, 1.0 equiv.) using 100 μL of BrF(Fs)2 borane catalyst solution (6.54 mg dissolved in 100 μL of anhydrous toluene) according to general procedure E. The reaction was complete after stirring overnight. The crude product was purified by flash column chromatography with gradient elution (20–65% DCM in petroleum ether) to afford 1-bromo-8,8-dimethyl-10-propyl-7,9,11-trioxa-8-silatricosane (1.38 g, 2.79 mmol, 96% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 4.81 (dd, 1H), δ3.70-3.63 (m, 3H), δ 3.40 (t, 2H), δ 3.34-3.29 (m, 1H), δ1.90-1.83 (m, 2H), δ 1.68-1.21 (br. m, 30H), δ 0.93-0.86 (m, 6H), δ 0.16 (d, 6H) Example 71 Synthesis of 13-bromo-6,6-dimethyl-4-nonyl-3,5,7-trioxa-6-silatridecane [ka]

[0147] 13-Bromo-6,6-dimethyl-4-nonyl-3,5,7-trioxa-6-silatridecane was prepared from ethyl decanoate (400 mg, 1.997 mmol, 1.0 equiv.) and ((6-bromohexyl)oxy)dimethylsilane (525.46 mg, 2.196 mmol, 1.1 equiv.) using 100 μL of BrF(Fs)2 borane catalyst solution (4.46 mg dissolved in 100 μL of anhydrous toluene) according to general procedure E. The reaction was complete after stirring overnight. The crude product was filtered through a short silica gel column to give a clear oil, 13-bromo-6,6-dimethyl-4-nonyl-3,5,7-trioxa-6-silatridecane (883 mg, 1.51 mmol, 75% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.04 (dt, 1H), δ 3.89 (m, 1H), δ 3.76 (t, 2H), δ 3.48 (m, 1H), δ 3.06 (t, 2H), δ2.01-1.93 (m, 2H), δ 1.70-1.52 (m, 6H), δ 1.51-1.33 (m, 12H), δ 1.28 (m, 7H), δ 1.01 (t, 3H), δ 0.33 (d, 6H) Example 72 Synthesis of 13-bromo-6,6-dimethyl-4-undecyl-3,5,7-trioxa-6-silatridecane [ka]

[0148] 13-Bromo-6,6-dimethyl-4-undecyl-3,5,7-trioxa-6-silatridecane was prepared from ethyl dodecanoate (1500 mg, 6.568 mmol, 1.0 equiv.) and ((6-bromohexyl)oxy)dimethylsilane (1493 mg, 6.240 mmol, 0.95 equiv.) using 100 μL of BrF(Fs)2 borane catalyst solution (29.36 mg dissolved in 100 μL of anhydrous toluene) according to general procedure E. The reaction was complete after stirring overnight. The crude product was filtered through a short silica gel column to give a clear oil, 13-bromo-6,6-dimethyl-4-undecyl-3,5,7-trioxa-6-silatridecane (3.04 g, 5.66 mmol, 86% yield). 1 H NMR (500 MHz, Toluene-d8) δ 4.92 (t, 1H), δ 3.81-3.73 (m, 1H), δ 3.63 (t, 2H), δ 3.39-3.32 (m, 1H), δ 2.95 (t, 2H), δ 1.88-1.74 (m, 2H), δ 1.61-1.10 (br. m, 29H), δ 0.90 (t, 3H), δ 0.21 (d, 6H) Example 73 Synthesis of 15-bromo-8,8-dimethyl-6-nonyl-5,7,9-trioxa-8-silapentadecane [ka]

[0149] 15-Bromo-8,8-dimethyl-6-nonyl-5,7,9-trioxa-8-silapentadecane was prepared from butyl decanoate (400 mg, 1.75 mmol) and ((6-bromohexyl)oxy)dimethylsilane (460.91 g, 1.93 mmol, 1.1 equiv.) using 100 μL of BrF(Fs)2 borane catalyst solution (7.83 mg dissolved in 100 μL of anhydrous toluene) according to general procedure E. The reaction was complete after stirring overnight. The crude product was filtered through a short silica gel column to give a clear oil, 1-15-bromo-8,8-dimethyl-6-nonyl-5,7,9-trioxa-8-silapentadecane (745 mg, 1.45 mmol, 83% yield). 1 H NMR (500 MHz, benzene-d6) δ 4.97 (dt, 1H), δ3.86-3.77 (m, 1H), δ 3.67 (t, 2H), δ 3.43-3.32 (m, 1H), δ 2.96 (t, 2H), δ 1.93-1.76 (m, 2H), δ 1.66-1.10 (br. m, 26H), δ 0.91 (t, 6H), δ 0.25 (d, 6H) Example 74 Synthesis of 15-bromo-8,8-dimethyl-6-undecyl-5,7,9-trioxa-8-silapentadecane [ka]

[0150] 15-Bromo-8,8-dimethyl-6-undecyl-5,7,9-trioxa-8-silapentadecane was prepared from butyl dodecanoate (200 mg, 0.78 mmol) and ((6-bromohexyl)oxy)dimethylsilane (205.24 mg, 0.858 mmol, 1.1 equiv.) using 100 μL of BrF(Fs)2 borane catalyst solution (0.70 mg dissolved in 100 μL of anhydrous toluene) according to general procedure E. The reaction was complete after stirring overnight. The crude product was filtered through a short silica gel column to give a clear oil, 15-bromo-8,8-dimethyl-6-undecyl-5,7,9-trioxa-8-silapentadecane (415 mg, 0.78 mmol, 100% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.01 (dt, 1H), δ3.90-3.82 (m, 1H), δ 3.72 (t, 2H), δ 3.46-3.39 (m, 1H), δ 3.02 (t, 2H), δ 2.00-1.79 (m, 2H), δ 1.70-1.15 (br. m, 30H), δ 0.99-0.93 (m, 6H), δ 0.29 (d, 6H) Example 75 Synthesis of 13-bromo-4,6,6-trimethyl-3,5,7-trioxa-6-silatridecane [ka]

[0151] 13-Bromo-4,6,6-trimethyl-3,5,7-trioxa-6-silatridecane was prepared from ethyl acetate (200 mg, 2.27 mmol) and ((6-bromohexyl)oxy)dimethylsilane (597.35 mg, 2.50 mmol, 1.1 equiv.) using 100 μL of BrF(Fs)2 borane catalyst solution (5.07 mg dissolved in 100 μL of anhydrous toluene) according to general procedure E. The reaction was complete after stirring overnight. The crude product was purified by flash column chromatography with gradient elution (0–30% EtOAc and 1% TEA in petroleum ether) to give 13-bromo-4,6,6-trimethyl-3,5,7-trioxa-6-silatridecane (325 mg, 0.99 mmol, 44% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 5.01 (q, 1H), δ3.80-3.66 (m, 1H), δ 3.61 (t, 2H), δ 3.36-3.26 (m, 1H), δ 2.95 (t, 2H), δ 1.56-1.36 (m, 7H), δ 1.20-1.10 (m, 7H), δ 0.18 (s, 6H) Example 76 Synthesis of 1-bromo-9-heptyl-7,7-dimethyl-6,8,10-trioxa-7-silaoctadecane [ka]

[0152] 1-Bromo-9-heptyl-7,7-dimethyl-6,8,10-trioxa-7-silaoctadecane was prepared from octyl octanoate (1.54 mg, 6.0 mmol) and ((5-bromopentyl)oxy)dimethylsilane (1.486 mg, 6.6 mmol, 1.1 equiv.) using 100 μL of BrF(Fs)2 borane catalyst solution (2.9 mg dissolved in 100 μL of anhydrous toluene) according to general procedure E. The reaction was complete after stirring overnight. The crude product was purified by flash column chromatography with gradient elution (0–5% EtOAc in petroleum ether) to give 1-bromo-9-heptyl-7,7-dimethyl-6,8,10-trioxa-7-silaoctadecane (2.63 g, 5.46 mmol, 91% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 5.08 (q, 1H), δ3.97-3.90 (m, 1H), δ 3.73 (t, 2H), δ 3.54-3.47 (m, 1H), δ 3.07 (t, 2H), δ 2.05-1.84 (m, 2H), δ 1.81-1.27 (br. m, 28H), δ 1.05-0.95 (m, 6H), δ 0.35 (d, 6H) Example 77 Synthesis of 1-bromo-10-heptyl-8,8-dimethyl-7,9-dioxa-11-thia-8-silaoctadecane [ka]

[0153] 1-Bromo-10-heptyl-8,8-dimethyl-7,9-dioxa-11-thia-8-silaoctadecane was prepared from octyl octanethioate (817.47 mg, 3.00 mmol) and ((6-bromohexyl)oxy)dimethylsilane (789.44 mg, 3.30 mmol, 1.1 equiv.) using 100 μL of BrF(Fs)2 borane catalyst solution (1.34 mg dissolved in 100 μL of anhydrous toluene) according to general procedure E. The reaction was complete after stirring overnight. The crude product was purified by flash column chromatography with gradient elution (20–65% DCM in petroleum ether) to give 1-bromo-10-heptyl-8,8-dimethyl-7,9-dioxa-11-thia-8-silaoctadecane (1.40 g, 2.74 mmol, 91% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 5.09 (t, 1H), δ3.74-3.67 (m, 2H), δ 3.00-2.92 (m, 2H), δ 2.81-3.63 (m, 2H), δ2.09-1.85 (m, 2H), δ 1.75-1.06 (br. m, 24H), δ 0.92-0.81 (m, 10H), δ 0.29 (d, 6H) Example 78 Synthesis of (Z)-1-bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silaicosar-17-ene [ka]

[0154] (Z)-1-Bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silicacosar-17-ene was prepared from (Z)-non-6-en-1-yl octanoate (1.0 g, 3.725 mmol) and ((6-bromohexyl)oxy)dimethylsilane (891.18 mg, 3.725 mmol, 1.0 equiv.) using 100 μL of BrF(Fs)2 borane catalyst solution (16.65 mg dissolved in 100 μL of anhydrous toluene) according to general procedure E. The reaction was complete after stirring overnight. The crude product was filtered through a short silica gel column to give a clear oil (Z)-1-bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silicacosar-17-ene (1.66 g, 3.14 mmol, 84% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.49-5.36 (m, 2H), δ 4.97 (dd, 1H), δ 3.86-3.79 (m, 1H), δ 3.67 (t, 2H), δ 3.42-3.34 (m, 1H), δ 2.96 (t, 2H), δ 2.08-1.97 (m, 4H), δ 1.92-1.75 (m, 2H), δ 1.69-1.08 (br. m, 24H), δ 0.96-0.87 (m, 6H), δ 0.25 (d, 6H) Example 79 Synthesis of (Z)-1-bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silaicosar-14-ene [ka]

[0155] (Z)-1-Bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silicacosar-14-ene was prepared from (Z)-non-3-en-1-yl octanoate (xxx g, xxx mmol) and ((6-bromohexyl)oxy)dimethylsilane (891.18 mg, 3.725 mmol, 1.0 equiv.) using 100 μL of BrF(Fs)2 borane catalyst solution (16.65 mg dissolved in 100 μL of anhydrous toluene) according to general procedure E. The reaction was complete after stirring overnight. The crude product was filtered through a short silica gel column to give a clear oil (Z)-1-bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silicacos-14-ene (1.81 g, 3.30 mmol, 89% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.63-5.49 (m, 2H), δ 4.98 (dd, 1H), δ 3.90-3.82 (m, 1H), δ 3.67 (t, 2H), δ 3.48-3.40 (m, 1H), δ 2.96 (t, 2H), δ 2.49-2.43 (m, 2H), δ 2.11-2.03 (m, 2H), δ 1.61-1.40 (m, 6H), δ1.38-1.10 (br. m, 20H), δ0.96-0.84 (m, 6H), δ 0.25 (d, 6H) Example 80 Synthesis of 10-bromo-3-((8Z,11Z)-heptadeca-8,11-dien-1-yl)-5,5-dimethyl-2,4,6-trioxa-5-siladecane [ka]

[0156] 10-Bromo-3-((8Z,11Z)-heptadeca-8,11-dien-1-yl)-5,5-dimethyl-2,4,6-trioxa-5-siladecane was prepared from methyl (9Z,12Z)-octadeca-9,12-dienoate (395.00 mg, 1.341 mmol) and ((4-bromobutyl)oxy)dimethylsilane (311.59 mg, 1.476 mmol, 1.1 equiv.) using 100 μL of BrF(Fs)2 borane catalyst solution (6.00 mg dissolved in 100 μL of anhydrous toluene) according to general procedure E. The reaction was complete after stirring overnight. The crude product was purified by flash column chromatography with gradient elution (0–100% EtOAc in n-hexane) to give 10-bromo-3-((8Z,11Z)-heptadeca-8,11-dien-1-yl)-5,5-dimethyl-2,4,6-trioxa-5-siladecane (390 mg, 0.77 mmol, 58% yield) as a clear oil. 1 H NMR (500 MHz, benzene-d6) δ 5.53-5.40 (m, 4H), δ 4.77 (t, 1H), δ 3.52 (t, 2H), δ 3.24 (s, 3H), δ 3.01 (t, 2H), δ 2.87 (t, 2H), δ 2.12-2.01 (m, 4H), δ 1.85-1.61 (m, 2H), δ 1.53-1.07 (br. m, 20H), δ 0.94-0.79 (m, 3H), δ 0.15 (s, 6H)

[0157] Chromatographic methods for purifying lipids and intermediates Purification method A Eluent A: DCM:MeOH:NH3 (aq) (80:20:1), eluent B: DCM; full gradient A:B 0:100 → 100:0. Sample load approx. 200 mg; column size: 25 g SiO2. Prior to sample loading, the column was conditioned with approx. 400 mL of A followed by approx. 400 mL of B.

[0158] Purification method B Eluent A: EtOAc, eluent B: petroleum ether + 1% Et3N; full gradient A:B 0:100 → 100:0. Sample load approx. 200 mg; column size: 25 g SiO2. Prior to sample loading, the column was conditioned with approx. 400 mL of B.

[0159] Synthetic methods for synthesizing intermediates and lipids (general procedures G-P) General Procedure G A MW reaction vial was charged with 1.0 equivalent of ω-bromoalkylsilyl mixed acetal, 1.0 equivalent of amine, anhydrous acetonitrile (1.0 mmol of ω-bromoalkylsilyl mixed acetal / 1.54 ml of anhydrous acetonitrile), and anhydrous cyclopentyl methyl ether (1.0 mmol of ω-bromoalkylsilyl mixed acetal / 0.51 ml of anhydrous cyclopentyl methyl ether). To the stirred reaction mixture, K2CO3 (2.0 equivalents) and KI (0.5 equivalents) were added, purged with argon, and sealed. The resulting mixture was stirred at 80 °C for 8 hours. The reaction mixture was then cooled to room temperature, partitioned between ethyl acetate and brine, and vigorously stirred for 15 minutes. The organic phase was separated, dried over Na2SO4, filtered, and concentrated.

[0160] General Procedure H A MW reaction vial was charged with 2.5 equivalents of ω-bromoalkylsilyl mixed acetal, 1.0 equivalent of amine, 2.5 equivalents of diisopropylethylamine, and absolute ethanol (1.0 mmol of ω-bromoalkylsilyl mixed acetal / 2.4 ml of absolute ethanol), purged with argon, and sealed. The resulting mixture was stirred at 63°C for 18 hours. The reaction mixture was then cooled to room temperature, partitioned between ethyl acetate and brine, and stirred vigorously for 15 minutes. The organic phase was separated, dried over NaSO, filtered, and concentrated.

[0161] General Procedure I A MW reaction vial was charged with 2.5 equivalents of ω-bromoalkylsilyl mixed acetal, 1.0 equivalent of amine, anhydrous acetonitrile (1.0 mmol of ω-bromoalkylsilyl mixed acetal / 0.95 ml of anhydrous acetonitrile), and anhydrous cyclopentyl methyl ether (1.0 mmol of ω-bromoalkylsilyl mixed acetal / 0.31 ml of anhydrous cyclopentyl methyl ether). To the stirred reaction mixture, K2CO3 (3.0 equivalents) and KI (0.2 equivalents) were added, purged with argon, and sealed. The resulting mixture was stirred at 60 °C for 18 h. The reaction mixture was then cooled to room temperature, partitioned between ethyl acetate and brine, and vigorously stirred for 15 min. The organic phase was separated, dried over Na2SO4, filtered, and concentrated.

[0162] General procedure J A MW reaction vial was charged with 1.0 equivalent of aldehyde, 1.0 equivalent of amine, 1.0 equivalent of acetic acid, and anhydrous toluene (1.0 mmol of aldehyde / 6.5 ml of anhydrous toluene). After stirring for 15 minutes, 3.0 equivalents of sodium triacetoxyborohydride were added, and the resulting mixture was stirred overnight. The reaction mixture was then diluted with ethyl acetate and NaHCO3 solution, stirred vigorously for 5 minutes, and the phases were allowed to separate. The organic phase was washed with brine, separated, dried over Na2SO4, filtered, and concentrated.

[0163] General Procedure K A MW reaction vial was charged with the ω-bromoalkylsilyl mixed acetal, amine, anhydrous acetonitrile (1.0 mmol of ω-bromoalkylsilyl mixed acetal / 4.0 mL of anhydrous acetonitrile), and anhydrous cyclopentyl methyl ether (ω-bromoalkylsilyl mixed acetal / 1.33 mL of anhydrous cyclopentyl methyl ether). To the stirred reaction mixture, K2CO3 (2.0 equiv.) and KI (0.2 equiv.) were added, purged with argon, and sealed. The resulting mixture was stirred at 62 °C for 18 h. The reaction mixture was then cooled to room temperature, partitioned between ethyl acetate and brine, and stirred vigorously for 15 min. The organic phase was separated, dried over Na2SO4, filtered, and concentrated.

[0164] General procedure L A MW reaction vial was charged with 1.0 equivalent of ω-bromoalkylsilyl mixed acetal, 20 equivalents of amine, 2.0 equivalents of K2CO3, and absolute ethanol (1.0 mmol of ω-bromoalkylsilyl mixed acetal / 0.32 ml of absolute ethanol), purged with argon, and sealed. The resulting mixture was stirred at room temperature overnight. The reaction mixture was then partitioned between ethyl acetate and brine and stirred vigorously for 15 minutes. The organic phase was separated, dried over Na2SO4, filtered, and concentrated.

[0165] General procedure M A MW reaction vial was charged with 1.0 equivalent of the mixed silyl acetal, 3.0 equivalents of the amine, tetrahydrofuran (1.0 mmol of the mixed silyl acetal / 4.5 ml of tetrahydrofuran), and water (1.0 mmol of the mixed silyl acetal / 0.9 ml of water). 3.0 equivalents of trifluoroacetic acid were added to the reaction mixture and stirred for 6 hours. 2.3 equivalents of sodium triacetoxyborohydride were then added to the reaction mixture and stirred at 60°C overnight. The reaction mixture was cooled to room temperature, diluted with saturated NaHCO3 solution, and extracted with ethyl acetate. The organic phase was washed with brine, separated, dried over Na2SO4, filtered, and concentrated.

[0166] General Procedure N A MW reaction vial was charged with 1.0 equivalent of ω-bromoalkyl ester, amine, 0.2 equivalents of KI, 2.2 equivalents of K2CO3, and anhydrous DMF (1.0 mmol of ω-bromoalkyl ester / 8.73 ml of anhydrous DMF), purged with argon, and sealed. The resulting mixture was stirred at 63 °C for 18 hours. The reaction mixture was then cooled to room temperature, diluted with saturated NaHCO3 solution, and extracted with ethyl acetate. The organic phase was washed with saturated NaHCO3 solution, brine, separated, dried over Na2SO4, filtered, and concentrated.

[0167] General Procedure A MW reaction vial was charged with 2.5 equivalents of ω-bromoalkylsilyl mixed acetal, 1.0 equivalent of amine, 3.0 equivalents of KCO, 0.2 equivalents of KI, and anhydrous DMF (1.0 mmol of ω-bromoalkylsilyl mixed acetal / 2.6 ml of anhydrous DMF), purged with argon, and sealed. The resulting mixture was stirred at 64° C. for 24 hours. The reaction mixture was then concentrated to dryness under vacuum, and the residue was purified by flash column chromatography.

[0168] General procedure P A MW reaction vial was charged with 1.0 equivalent of the propargylamine derivative, 1.5 equivalents of the azide derivative, 0.33 equivalents of CuBr, 0.33 equivalents of 1,1,4,7,7-pentamethyldiethylenetriamine, and anhydrous DMF (0.1 mmol of the propargylamine derivative / 3.0 ml of anhydrous DMF), purged with argon, and sealed. The resulting mixture was stirred at 50° C. for 20 hours. The reaction mixture was then concentrated to dryness under vacuum, and the residue was purified by flash column chromatography. Intermediate synthesis example Example 81 Synthesis of 4-((6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)amino)butan-1-ol [ka]

[0169] 4-((6-((Dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)amino)butan-1-ol was prepared from ((6-bromo-1-(octyloxy)hexyl)oxy)dimethyl(octyl)silane (300.0 mg, 0.625 mmol, 1.0 equiv.) and 4-amino-1-butanol (1115.01 mg, 12.51 mmol, 20.0 equiv.) according to general procedure L. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (100.0 mg, 0.205 mmol, 33% yield). 1H NMR (500 MHz, benzene-d6) δ 4.89 (t, 1H), δ3.78-3.73 (m, 1H), δ 3.65-3.62 (m, 2H), δ 3.39-3.34 (m, 1H), δ2.31-2.27 (m, 4H), δ 1.83-1.20 (m, 36H), δ 0.94-0.88 (m, 6H), δ0.76-0.72 (m, 2H), δ 0.26 (d, 6H) Example 82 Synthesis of 13-heptyl-15,15-dimethyl-12,14-dioxa-5-aza-15-silatricosan-1-ol [ka]

[0170] 13-Heptyl-15,15-dimethyl-12,14-dioxa-5-aza-15-silatricosan-1-ol was prepared from ((1-((6-bromohexyl)oxy)octyl)oxy)dimethyl(octyl)silane (300.0 mg, 0.625 mmol, 1.0 equiv.) and 4-amino-1-butanol (1115.01 mg, 12.51 mmol, 20.0 equiv.) according to general procedure L. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (95.0 mg, 0.195 mmol, 31% yield). 1 H NMR (500 MHz, benzene-d6) δ 4.89 (t, 1H), δ3.77-3.71 (m, 1H), δ 3.64-3.61 (m, 2H), δ 3.39-3.32 (m, 1H), δ2.30-2.29 (m, 4H), δ 1.87-1.18 (m, 36H), δ 0.92-0.88 (m, 6H), δ0.75-0.71 (m, 2H), δ 0.25 (d, 6H) Example 83 Synthesis of 4-((6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)hexyl)amino)butan-1-ol [ka]

[0171] 4-((6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)hexyl)amino)butan-1-ol was prepared from 1-((6-bromo-1-(octyloxy)hexyl)oxy)-1,1,3,3-tetramethyl-3-(octyloxy)disiloxane (100.00 mg, 0.175 mmol, 1.0 equiv.) and 4-amino-1-butanol (312.87 mg, 3.509 mmol, 20.0 equiv.) according to general procedure L. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (75.0 mg, 0.130 mmol, 74% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.03 (t, 1H), δ3.93-3.84 (m, 1H), δ 3.78-3.75 (t, 2H), δ 3.64-3.61 (m, 2H), δ 3.49-3.35 (m, 1H), δ 2.36-2.25 (m, 4H), δ 1.93-1.17 (m, 36H), δ 0.92-0.88 (m, 6H), δ 0.31 (d, 6H), δ 0.25 (s, 6H) Example 84 Synthesis of 15-heptyl-13,13-dimethyl-12,14,16-trioxa-5-aza-13-silatetracosan-1-ol [ka]

[0172] 15-Heptyl-13,13-dimethyl-12,14,16-trioxa-5-aza-13-silatetracosan-1-ol was prepared from 1-bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silanonadecane (500.0 mg, 1.010 mmol, 1.0 equiv) and 4-amino-1-butanol (1.798 g, 20.175 mmol, 20.0 equiv) according to general procedure L. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (200.0 mg, 0.397 mmol, 40% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.01 (t, 1H), δ3.93-3.79 (m, 1H), δ 3.75 (t, 2H), δ 3.61 (t, 1H), δ3.44-3.40 (m, 2H), δ 2.32-2.27 (m, 2H), δ 1.96-1.14 (m, 38H), δ0.93-0.87 (m, 6H), δ 0.28 (d, 6H) Example 85 Synthesis of 4-(((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)amino)butan-1-ol [ka]

[0173] 4-(((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)amino)butan-1-ol was prepared from (((5Z,8Z,11Z,14Z,17Z)-1-ethoxyicosa-5,8,11,14,17-pentaen-1-yl)oxy)triethylsilane (1478.20 mg, 3.309 mmol, 1.0 equiv.) and 4-amino-1-butanol (884.74 mg, 9.925 mmol, 3.0 equiv.) according to general procedure M. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (983.0 mg, 2.734 mmol, 83% yield). 1 H NMR (500 MHz, CDCl3) δ5.43-5.27 (m, 10H), δ 3.98 (broad s, 2H), δ 3.57 (m, 2H), δ2.88-2.76 (m, 8H), δ 2.68-2.61 (m, 4H), δ 2.12-2.03 (m, 4H), δ1.71-1.60 (m, 4H), δ 1.57-1.48 (m, 2H), δ 1.43-1.35 (m, 2H), δ 0.97 (t, 3H) Example 86 Synthesis of 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate [ka]

[0174] 6-((4-Hydroxybutyl)amino)hexyl 2-hexyldecanoate was prepared from 6-ethoxy-6-((triethylsilyl)oxy)hexyl 2-hexyldecanoate (1488.4 mg, 2.891 mmol, 1.0 equiv.) and 4-amino-1-butanol (772.99 mg, 8.672 mmol, 3.0 equiv.) according to general procedure M. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (1056 mg, 2.469 mmol, 85% yield). 1 H NMR (500 MHz, CDCl3) δ 4.05 (t, 2H), δ 3.56 (m, 2H), δ 2.65-2.58 (m, 4H), δ 2.33-2.26 (m, 1H), δ1.70-1.19 (m, 36H), δ 0.88-0.85 (dt, 6H) Example 87 Synthesis of 6-((3-hydroxypropyl)amino)hexyl 2-hexyldecanoate [ka]

[0175] 6-((3-Hydroxypropyl)amino)hexyl 2-hexyldecanoate was prepared from 6-ethoxy-6-((triethylsilyl)oxy)hexyl 2-hexyldecanoate (1500 mg, 2.913 mmol, 1.0 equiv.) and 3-aminopropanol (656.43 mg, 8.740 mmol, 3.0 equiv.) according to general procedure M. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (1265.0 mg, 1.651 mmol, 57% yield). 1 H NMR (500 MHz, CDCl3) δ 4.03 (t, 2H), δ 3.79 (t, 2H), δ 2.92 (t, 2H), δ 2.35-2.25 (m, 1H), δ1.95-1.90 (t, 2H), δ 1.74-1.18 (m, 34H), δ 0.86 (t, 6H) Example 88 Synthesis of 6-((2-hydroxyethyl)amino)hexyl 2-hexyldecanoate [ka]

[0176] 6-((2-Hydroxyethyl)amino)hexyl 2-hexyldecanoate was prepared from 6-ethoxy-6-((triethylsilyl)oxy)hexyl 2-hexyldecanoate (1000 mg, 1.942 mmol, 1.0 equiv.) and 2-amino-1-ethanol (355.9 mg, 5.827 mmol, 3.0 equiv.) according to general procedure M. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (590.0 mg, 1.476 mmol, 76% yield). 1H NMR (500 MHz, CDCl3) δ 4.04 (t, 2H), δ 3.86 (t, 2H), δ 3.08-3.05 (m, 2H), δ 2.95 (t, 2H), δ2.34-2.24 (m, 1H), δ 1.77-1.12 (m, 32H), δ 0.86 (t, 6H) Example 89 Synthesis of 6-((2-(1-methylpyrrolidin-2-yl)ethyl)amino)hexyl 2-hexyldecanoate [ka] 6-((2-(1-methylpyrrolidin-2-yl)ethyl)amino)hexyl 2-hexyldecanoate was reacted with 6-ethoxy-6-((triethylsilyl)oxy)hexyl 2-hexyldecanoate (850 mg, 1.651 mmol, 1.0 equiv.) and 2-(1-methylpyrrolidine- Prepared from (2-yl)ethan-1-amine (634.98 mg, 4.953 mmol, 3.0 equiv.) according to general procedure M. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (120.0 mg, 0.257 mmol, 16% yield). 1 H NMR (500 MHz, CDCl3) δ 4.03 (t, 2H), δ 3.27-3.22 (m, 1H), δ 3.01-2.87 (m, 2H), δ 2.82-2.75 (m, 1H), δ 2.54 (s, 3H), δ 2.49-2.43 (m, 1H), δ 2.33-2.25 (m, 2H), δ 2.16-2.07 (m, 1H), δ2.04-1.17 (br. m, 38H), δ 0.86 (t, 6H) Example 90 Synthesis of 6-((4-hydroxybutyl)amino)hexyl 2-(pentylthio)decanoate [ka]

[0177] 6-((4-Hydroxybutyl)amino)hexyl 2-(pentylthio)decanoate was prepared from 6-methoxy-6-((triethylsilyl)oxy)hexyl 2-(pentylthio)decanoate (1500.00 mg, 2.891 mmol, 1.0 equiv.) and 4-amino-1-butanol (772.99 mg, 8.672 mmol, 3.0 equiv.) according to general procedure M. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (1123.0 mg, 2.519 mmol, 87% yield). 1 H NMR (500 MHz, CDCl3) δ 4.11 (t, 2H), δ 3.56 (t, 2H), δ 3.22-3.19 (m, 1H), δ 2.65-2.42 (m, 6H), δ1.89-1.80 (m, 1H), δ 1.70-1.16 (m, 31H), δ 0.90-0.85 (dt, 6H) Example 91 Synthesis of 6-((4-hydroxybutyl)amino)hexyl 2-(decylthio)hexanoate [ka]

[0178] 6-((4-Hydroxybutyl)amino)hexyl 2-(decylthio)hexanoate was prepared from 6-methoxy-6-((triethylsilyl)oxy)hexyl 2-(decylthio)hexanoate (400.00 mg, 0.751 mmol, 1.0 equiv.) and 4-amino-1-butanol (200.71 mg, 2.252 mmol, 3.0 equiv.) according to general procedure M. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (211.0 mg, 0.459 mmol, 61% yield). 1H NMR (500 MHz, CDCl3) δ 4.12 (t, 2H), δ 3.56 (m, 2H), δ 3.22-3.19 (m, 1H), δ 2.66-2.51 (m, 6H), δ1.90-1.81 (m, 1H), δ 1.70-1.20 (m, 33H), δ 0.91-0.86 (dt, 6H) Example 92 Synthesis of 4-(((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentyl)amino)butan-1-ol [ka]

[0179] 4-(((4R)-4-((3R,10S,13R)-3-Methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentyl)amino)butan-1-ol was prepared from triethyl(((4R)-1-methoxy-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentyl)oxy)silane (237.00 mg, 0.455 mmol, 1.0 equiv) and 4-amino-1-butanol (121.67 mg, 1.365 mmol, 3.0 equiv) according to general procedure M. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (178.0 mg, 0.398 mmol, 87% yield). 1 H NMR (500 MHz, CDCl3) δ 4.62 (m, 1H), δ 3.76 (s, 3H), δ 3.57 (t, 2H), δ 2.66-2.63 (m, 2H), δ2.61-2.49 (m, 2H), δ 1.97-1.02 (m, 32H), δ 0.92-0.89 (m, 6H), δ 0.63 (s, 3H) Example 93 Synthesis of 4-((4-hydroxybutyl)amino)butyl (4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentanoate [ka]

[0180] 4-((4-Hydroxybutyl)amino)butyl (4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentanoate was prepared according to general procedure K from 4-chlorobutyl (4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentanoate (237.00 mg, 0.455 mmol, 1.0 equiv) and 4-aminobutanol (121.67 mg, 1.365 mmol, 3.0 equiv). The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (194.0 mg, 0.364 mmol, 80% yield). 1 H NMR (500 MHz, CDCl3) δ 4.05 (m, 2H), δ 3.60 (t, 2H), δ 3.35 (s, 3H), δ 3.18-3.11 (m, 1H), δ2.90-2.85 (q, 2H), δ 2.80-2.71 (q, 3H), δ 2.36-2.29 (m, 1H), δ2.22-2.14 (m, 1H), δ 1.93-1.50 (br. m, 16H), δ 1.44-0.88 (br. m, 18H), δ 0.90-0.88 (m, 6H), δ 0.62 (s, 3H) Example 94 Synthesis of undecyl 6-((2-hydroxyethyl)amino)hexanoate [ka]

[0181] Undecyl 6-((2-hydroxyethyl)amino)hexanoate was prepared from undecyl 6-bromohexanoate (1000.00 mg, 2.862 mmol, 1.0 equiv) and 2-amino-1-ethanol (192.33 mg, 3.148 mmol, 1.1 equiv) according to general procedure N. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (350.0 mg, 1.062 mmol, 37% yield). 1 H NMR (500 MHz, CDCl3) δ 4.04 (t, 2H), δ 3.63 (m, 2H), δ 2.76 (m, 2H), δ 2.61 (t, 2H), δ 2.29 (t, 2H), δ 2.09 (broad s, 2H), δ 1.67-1.57 (m, 4H), δ 1.54-1.47 (m, 2H), δ1.39-1.22 (m, 18H), δ 0.87 (t, 3H) Example 95 Synthesis of undecyl 6-((4-hydroxybutyl)amino)hexanoate [ka]

[0182] Undecyl 6-((4-hydroxybutyl)amino)hexanoate was prepared from undecyl 6-bromohexanoate (1124.21 mg, 3.218 mmol, 1.0 equiv) and 4-amino-1-butanol (5737.05 mg, 64.36 mmol, 20 equiv) according to general procedure N. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a thick yellow oil (969.0 mg, 2.607 mmol, 81% yield). 1H NMR (500 MHz, CDCl3) δ 4.03 (t, 2H), δ 3.57 (t, 2H), δ 2.71-2.63 (m, 4H), δ 2.29 (t, 2H), δ1.69-1.52 (m, 10H), δ 1.40-1.19 (m, 18H), δ 0.86 (t, 3H) Example 96 Synthesis of heptadecan-9-yl 8-((2-hydroxyethyl)amino)octanoate [ka]

[0183] Heptadecan-9-yl 8-((2-hydroxyethyl)amino)octanoate was prepared from heptadecan-9-yl 8-bromooctanoate (200.00 mg, 0.412 mmol, 1.0 equiv.) and 2-amino-1-ethanol (27.66 mg, 0.453 mmol, 1.1 equiv.) according to general procedure N. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (100.0 mg, 0.226 mmol, 55% yield). 1 H NMR (500 MHz, CDCl3) δ4.89-4.83 (m, 1H), δ 3.62 (s, 2H), δ 2.78-2.75 (m, 2H), δ 2.60 (t, 2H), δ 2.27 (t, 2H), δ 1.65-1.56 (m, 2H), δ 1.53-1.41 (m, 6H), δ1.36-1.16 (m, 30H), δ 0.87 (t, 6H) Example 97 Synthesis of heptadecan-9-yl 8-((4-hydroxybutyl)amino)octanoate [ka]

[0184] Heptadecan-9-yl 8-((4-hydroxybutyl)amino)octanoate was prepared from heptadecan-9-yl 8-bromooctanoate (950 mg, 1.841 mmol, 1.0 equiv) and 4-amino-1-butanol (3.28 g, 36.83 mmol, 20 equiv) according to general procedure L. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (865.0 mg, 1.28 mmol, 69% yield). 1 H NMR (500 MHz, CDCl3) δ 5.19 (m, 1H), δ 3.80-3.76 (m, 2H), δ 3.48-3.40 (m, 2H), δ 2.61 (t, 2H), δ 2.51 (t, 2H), δ 2.28 (t, 2H), δ 1.83-1.10 (br. m, 40H), δ 0.98-0.91 (m, 6H) Example 98 Synthesis of 6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)-N-(prop-2-yn-1-yl)hexan-1-amine [ka]

[0185] A MW reaction vial was charged with ((6-bromo-1-(octyloxy)hexyl)oxy)dimethyl(octyl)silane (400 mg, 0.834 mmol, 1.0 equiv.), propargylamine hydrochloride (381.69 mg, 4.170 mmol, 5.0 equiv.), K2CO3 (806.79 mg, 5.838 mmol, 7.0 equiv.), KI (13.84 mg, 0.083 mmol, 0.1 equiv.), 1.5 ml of anhydrous acetonitrile, and 1.0 ml of cyclopentyl methyl ether, purged with argon, and sealed. The resulting mixture was stirred at 62 °C for 18 h. The reaction mixture was then cooled to room temperature, partitioned between ethyl acetate and brine, and stirred vigorously for 15 min. The organic phase was separated, dried over Na2SO4, filtered, and concentrated. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (260 mg, 0.573 mmol, 69% yield). 1 H NMR (500 MHz, benzene-d6) δ 4.85 (t, 1H), δ3.77-3.72 (q, 1H), δ 3.39-3.34 (q, 1H), δ 3.16 (d, 2H), δ 2.50 (t, 2H), δ 1.93 (t, 1H), δ 1.83-1.16 (m, 32H), δ 0.94-0.88 (m, 6H), δ0.75-0.71 (m, 2H), δ 0.24 (d, 6H) Example 99 Synthesis of 6-((dimethyl(octyl)silyl)oxy)-N-(6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)-6-(octyloxy)-N-(prop-2-yn-1-yl)hexan-1-amine [ka]

[0186] A MW reaction vial was charged with ((6-bromo-1-(octyloxy)hexyl)oxy)dimethyl(octyl)silane (431.22 mg, 0.899 mmol, 1.2 equiv.), 6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)-N-(prop-2-yn-1-yl)hexan-1-amine (340.00 mg, 0.749 mmol, 1.0 equiv.), KCO (207.09 mg, 1.499 mmol, 2.0 equiv.), KI (12.44 mg, 0.075 mmol, 0.1 equiv.), 1.5 mL of anhydrous acetonitrile, and 0.5 mL of cyclopentyl methyl ether, purged with argon, and sealed. The resulting mixture was stirred at 62 °C for 24 h. The reaction mixture was then cooled to room temperature, partitioned between ethyl acetate and brine, and stirred vigorously for 15 minutes. The organic phase was separated, dried over Na2SO4, filtered, and concentrated. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (530 mg, 0.622 mmol, 83% yield). 1 H NMR (500 MHz, benzene-d6) δ 4.87 (t, 2H), δ3.79-3.72 (q, 2H), δ 3.42-3.34 (q, 2H), δ 3.32 (d, 2H), δ 2.51 (t, 4H), δ 1.92 (t, 1H), δ 1.88-1.17 (m, 64H), δ 0.95-0.89 (m, 12H), δ0.75-0.71 (m, 4H), δ 0.25 (d, 12H) Example 100 Synthesis of 6-(octyloxy)-N-(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)hexyl)-N-(prop-2-yn-1-yl)-6-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)hexan-1-amine [ka]

[0187] A MW reaction vial was charged with 1-((6-bromo-1-(octyloxy)hexyl)oxy)-1,1,3,3-tetramethyl-3-octyldisiloxane (453.74 mg, 0.819 mmol, 2.5 equiv.), propargylamine hydrochloride (30.00 mg, 0.328 mmol, 1.0 equiv.), K2CO3 (181.18 mg, 1.311 mmol, 4.0 equiv.), KI (10.88 mg, 0.065 mmol, 0.2 equiv.), 1.2 ml of anhydrous acetonitrile, and 0.4 ml of cyclopentyl methyl ether, purged with argon, and sealed. The resulting mixture was stirred at 62 °C for 18 h. The reaction mixture was then cooled to room temperature, partitioned between ethyl acetate and brine, and stirred vigorously for 15 min. The organic phase was separated, dried over Na2SO4, filtered, and concentrated. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (83 mg, 0.083 mmol, 25% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.00 (t, 2H), δ3.90-3.83 (q, 2H), δ 3.46-3.38 (q, 2H), δ 3.33 (d, 2H), δ 2.52 (t, 4H), δ 1.92-1.17 (m, 65H), δ 0.95-0.89 (m, 12H), δ 0.71-0.66 (m, 4H), δ 0.27 (d, 12H), δ 0.22 (s, 12H), Example of lipid synthesis Example 101 Synthesis of 4-(bis(6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)amino)butan-1-ol [ka]

[0188] 4-(bis(6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)amino)butan-1-ol was prepared from ((6-bromo-1(octyloxy)hexyl)oxy)dimethyl(octyl)silane (93.4 mg, 0.195 mmol, 1.0 equiv.) and 4-((6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)amino)butan-1-ol (95.0 mg, 0.195 mmol, 1.0 equiv.) according to general procedure G. The crude product was purified twice by flash column chromatography according to purification methods A and B to give the pure product as a colorless oil (70 mg, 0.079 mmol, 40% yield). 1 H NMR (500 MHz, benzene-d6) δ 4.88 (t, 2H), δ3.79-3.72 (m, 2H), δ 3.62 (t, 2H), δ 3.41-3.36 (m, 2H), δ 2.33 (t, 4H), δ 2.24 (t, 2H), δ 1.77-1.25 (m, 68H), δ 0.94-0.89 (m, 12H), δ0.76-0.72 (m, 4H), δ 0.26 (d, 12H); TOF MS ES + [M+H + ]:886.8069 m / z Example 102 Synthesis of 5-(6-((1-((dimethyl(octyl)silyl)oxy)octyl)oxy)hexyl)-13-heptyl-15,15-dimethyl-12,14-dioxa-5-aza-15-silatricosan-1-ol [ka]

[0189] 5-(6-((1-((dimethyl(octyl)silyl)oxy)octyl)oxy)hexyl)-13-heptyl-15,15-dimethyl-12,14-dioxa-5-aza-15-silatricosan-1-ol was prepared from ((1-((6-bromohexyl)oxy)octyl)oxy)dimethyl(octyl)silane (147.47 mg, 0.307 mmol, 1.0 equiv.) and 13-heptyl-15,15-dimethyl-12,14-dioxa-5-aza-15-silatricosan-1-ol (150.00 mg, 0.307 mmol, 1.0 equiv.) according to general procedure G. The crude product was purified twice by flash column chromatography according to purification methods A and B to give the pure product as a colorless oil (100 mg, 0.113 mmol, 37% yield). 1 H NMR (500 MHz, benzene-d6) δ 4.89 (t, 2H), δ3.79-3.74 (m, 2H), δ 3.63 (t, 2H), δ 3.41-3.35 (m, 2H), δ 2.32 (m, 4H), δ 2.25 (t, 2H), δ 1.89-1.24 (m, 68H), δ 0.95-0.89 (m, 12H), δ0.77-0.72 (m, 4H), δ 0.26 (d, 12H); TOF MS ES + [M+H + ]:886.8039 m / z Example 103 Synthesis of 4-(bis(6-(decyloxy)-6-((hexyldimethylsilyl)oxy)hexyl)amino)butan-1-ol [ka]

[0190] 4-(bis(6-(decyloxy)-6-((hexyldimethylsilyl)oxy)hexyl)amino)butan-1-ol was prepared from ((6-bromo-1-(decyloxy)hexyl)oxy)(hexyl)dimethylsilane (403.27 mg, 0.841 mmol, 2.5 equiv.) and 4-amino-1-butanol (29.98 mg, 0.336 mmol, 1.0 equiv.) according to general procedure H. The crude product was purified twice by flash column chromatography according to purification methods A and B to give the pure product as a colorless oil (45 mg, 0.051 mmol, 15% yield). 1 H NMR (500 MHz, benzene-d6) δ 4.89 (t, 2H), δ3.80-3.74 (m, 2H), δ 3.63 (t, 2H), δ 3.43-3.36 (m, 2H), δ2.35-2.31 (m, 4H), δ 2.25 (t, TOF MS ES + [M+H + ]:886.8082 m / z Example 104 Synthesis of 5-(6-((1-((hexyldimethylsilyl)oxy)decyl)oxy)hexyl)-15,15-dimethyl-13-nonyl-12,14-dioxa-5-aza-15-silahenicosan-1-ol [ka]

[0191] 5-(6-((1-((hexyldimethylsilyl)oxy)decyl)oxy)hexyl)-15,15-dimethyl-13-nonyl-12,14-dioxa-5-aza-15-silahenicosan-1-ol was prepared from ((1-((6-bromohexyl)oxy)decyl)oxy)(hexyl)dimethylsilane (403.27 mg, 0.841 mmol, 2.5 equiv.) and 4-amino-1-butanol (30.00 mg, 0.336 mmol, 1.0 equiv.) according to general procedure H. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (45 mg, 0.051 mmol, 15% yield, 53 mg, 0.060 mmol, 18% yield). 1 H NMR (500 MHz, benzene-d6) δ 4.89 (t, 2H), δ3.78-3.73 (m, 2H), δ 3.63 (t, 2H), δ 3.41-3.35 (m, 2H), δ2.34-2.30 (m, 4H), δ 2.25 (t, TOF MS ES + [M+H + ]:886.8081 m / z Example 105 Synthesis of 5-(6-((dimethyl(octyloxy)silyl)oxy)-6-(octyloxy)hexyl)-13,13-dimethyl-11-(octyloxy)-12,14-dioxa-5-aza-13-siladocosan-1-ol [ka]

[0192] 5-(6-((dimethyl(octyloxy)silyl)oxy)-6-(octyloxy)hexyl)-13,13-dimethyl-11-(octyloxy)-12,14-dioxa-5-aza-13-siladocosane-1-ol was prepared from 12-(5-bromopentyl)-10,10-dimethyl-9,11,13-trioxa-10-silahenicosane (416.72 mg, 0.841 mmol, 2.5 equiv.) and 4-amino-1-butanol (29.98 mg, 0.336 mmol, 1.0 equiv.) according to general procedure I. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (187 mg, 0.204 mmol, 61% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.01(dt, 2H), δ3.89-3.84 (m, 2H), δ 3.77 (t, 4H), δ 3.62 (t, 2H), δ3.46-3.38 (m, 3H), δ 2.33 (m, 3H), δ 2.24 (t, 2H), δ1.98-1.78 (m, 4H), δ 1.71-1.19 (m, 64H) δ 0.93-0.88 (m, 12H), δ 0.28 (d, 12H); TOF MS ES + [M+H + ]:918.7984 m / z Example 106 Synthesis of 13-heptyl-5-(8-heptyl-10,10-dimethyl-7,9,11-trioxa-10-silanonadecyl)-15,15-dimethyl-12,14,16-trioxa-5-aza-15-silatetracosan-1-ol [ka]

[0193] 13-Heptyl-5-(8-heptyl-10,10-dimethyl-7,9,11-trioxa-10-silanonadecyl)-15,15-dimethyl-12,14,16-trioxa-5-aza-15-silatetracosan-1-ol was prepared from 1-bromo-8-heptyl-10,10-dimethyl-7,9,11-trioxa-10-silanonadecane (416.72 mg, 0.840 mmol, 2.5 equiv.) and 4-amino-1-butanol (29.98 mg, 0.336 mmol, 1.0 equiv.) according to general procedure I. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (146 mg, 0.159 mmol, 47% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.00 (dt, 2H), δ3.89-3.84 (m, 2H), δ 3.79 (t, 4H), δ 3.63 (t, 2H), δ3.45-3.38 (m, 2H), δ 2.34-2.30 (t, TOF MS ES + [M+H + ]:918.7991 m / z Example 107 Synthesis of 4-(bis(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)hexyl)amino)butan-1-ol [ka]

[0194] 4-(bis(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)hexyl)amino)butan-1-ol was prepared from 1-((6-bromo-1-(octyloxy)hexyl)oxy)-1,1,3,3-tetramethyl-3-octyldisiloxane (465.62 mg, 0.841 mmol, 2.5 equiv.) and 4-amino-1-butanol (29.98 mg, 0.336 mmol, 1.0 equiv.) according to general procedure H. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (87 mg, 0.084 mmol, 25% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.01 (dt, 2H), δ3.91-3.84 (m, 2H), δ 3.61 (t, 2H), δ 3.45-3.41 (m, 2H), δ2.35-2.32 (t, 4H), δ 2.25 (t, 2H), δ 1.96-1.77 (m, 4H), δ1.75-1.15 (m, 64H), δ 0.94-0.89 (m, 12H), δ 0.70-0.66 (m, 4H), δ 0.27 (d, 12H), δ 0.22 (s, 12H); TOF MS ES + [M+H + ]:1034.8458 m / z Example 108 Synthesis of 13-heptyl-15,15,17,17-tetramethyl-5-(6-((1-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)octyl)oxy)hexyl)-12,14,16-trioxa-5-aza-15,17-disilapentacosan-1-ol [ka]

[0195] 13-Heptyl-15,15,17,17-tetramethyl-5-(6-((1-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)octyl)oxy)hexyl)-12,14,16-trioxa-5-aza-15,17-disilapentacosan-1-ol was prepared from 1-((1-((6-bromohexyl)oxy)octyl)oxy)-1,1,3,3-tetramethyl-3-octyldisiloxane (465.62 mg, 0.841 mmol, 2.5 equiv.) and 4-amino-1-butanol (29.98 mg, 0.336 mmol, 1.0 equiv.) according to general procedure I. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (237 mg, 0.229 mmol, 66% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.01 (dt, 2H), δ3.88-3.83 (m, 2H), δ 3.63 (t, 2H), δ 3.45-3.38 (m, 2H), δ2.42-2.25 (m, 6H), δ 1.97-1.16 (m, 67H), δ 0.97-0.84 (m, 13H), δ0.74-0.61 (m, 4H), δ 0.28 (d, 12H), δ 0.22 (s, 12H); TOF MS ES + [M+H + ]:1034.8467 m / z Example 109 Synthesis of 4-(bis(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)hexyl)amino)butan-1-ol [ka]

[0196] 4-(bis(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)hexyl)amino)butan-1-ol was prepared from 1-((6-bromo-1-(octyloxy)hexyl)oxy)-1,1,3,3-tetramethyl-3-(octyloxy)disiloxane (319.90 mg, 0.561 mmol, 2.5 equiv.) and 4-amino-1-butanol (20.02 mg, 0.225 mmol, 1.0 equiv.) according to general procedure I. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (60 mg, 0.056 mmol, 25% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.03 (dt, 2H), δ3.91-3.85 (m, 2H), δ 3.76 (t, 4H), δ 3.61 (t, 2H), δ3.47-3.38 (m, 2H), δ 2.35-2.31 (t, TOF MS ES + [M+H + ]:1066.8368 m / z Example 110 Synthesis of 13-heptyl-15,15,17,17-tetramethyl-5-(6-((1-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)octyl)oxy)hexyl)-12,14,16,18-tetraoxa-5-aza-15,17-disilahexacosan-1-ol [ka]

[0197] 13-Heptyl-15,15,17,17-tetramethyl-5-(6-((1-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)octyl)oxy)hexyl)-12,14,16,18-tetraoxa-5-aza-15,17-disilahexacosan-1-ol was prepared from 1-((1-((6-bromohexyl)oxy)octyl)oxy)-1,1,3,3-tetramethyl-3-(octyloxy)disiloxane (319.90 mg, 0.561 mmol, 2.5 equiv) and 4-amino-1-butanol (20.02 mg, 0.225 mmol, 1.0 equiv) according to general procedure I. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (97 mg, 0.091 mmol, 41% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.04 (dt, 2H), δ3.90-3.84 (m, 2H), δ 3.76 (t, 4H), δ 3.62 (t, 2H), δ3.48-3.37 (m, 2H), δ 2.34-2.30 (m, TOF MS ES + [M+H + ]:1066.8358 m / z Example 111 Synthesis of 16-hexyl-5-(6-((((2-hexyldecyl)oxy)dimethylsilyl)oxy)-6-(octyloxy)hexyl)-13,13-dimethyl-11-(octyloxy)-12,14-dioxa-5-aza-13-silatetracosan-1-ol [ka]

[0198] 16-Hexyl-5-(6-((((2-hexyldecyl)oxy)dimethylsilyl)oxy)-6-(octyloxy)hexyl)-13,13-dimethyl-11-(octyloxy)-12,14-dioxa-5-aza-13-silatetracosan-1-ol was prepared from 10-(5-bromopentyl)-15-hexyl-12,12-dimethyl-9,11,13-trioxa-12-silatricosane (511.07 mg, 0.841 mmol, 2.5 equiv.) and 4-amino-1-butanol (29.98 mg, 0.336 mmol, 1.0 equiv.) according to general procedure I. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (269 mg, 0.232 mmol, 69% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.02 (dt, 2H), δ3.91-3.84 (m, 2H), δ 3.75-3.73 (d, 4H), δ 3.61 (t, 2H), 3.48-3.40 (m, 2H), δ 2.34 (t, TOF MS ES + [M fragment +H + ]:918.7993 m / z Example 112 Synthesis of 13-heptyl-5-(8-heptyl-13-hexyl-10,10-dimethyl-7,9,11-trioxa-10-silahenicosyl)-18-hexyl-15,15-dimethyl-12,14,16-trioxa-5-aza-15-silahexacosan-1-ol [ka]

[0199] 13-Heptyl-5-(8-heptyl-13-hexyl-10,10-dimethyl-7,9,11-trioxa-10-silahenicosyl)-18-hexyl-15,15-dimethyl-12,14,16-trioxa-5-aza-15-silahexacosan-1-ol was prepared from 1-bromo-8-heptyl-13-hexyl-10,10-dimethyl-7,9,11-trioxa-10-silahenicosane (511.46 mg, 0.841 mmol, 2.5 equiv.) and 4-amino-1-butanol (30.00 mg, 0.336 mmol, 1.0 equiv.) according to general procedure I. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (328 mg, 0.283 mmol, 84% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.01 (t, 2H), δ3.90-3.83 (m, 2H), δ 3.74-3.73 (d, 4H), δ 3.62 (t, 2H), 3.46-3.38 (m, 2H), δ 2.33 (t, TOF MS ES + [M fragment +H + ]:918.7980 m / z Example 113 Synthesis of 5-(6-(dimethyl((1-(octyloxy)octyl)oxy)silyl)hexyl)-14-heptyl-12,12-dimethyl-13,15-dioxa-5-aza-12-silatricosan-1-ol [ka]

[0200] 5-(6-(dimethyl((1-(octyloxy)octyl)oxy)silyl)hexyl)-14-heptyl-12,12-dimethyl-13,15-dioxa-5-aza-12-silatricosan-1-ol was prepared from (6-bromohexyl)dimethyl((1-(octyloxy)octyl)oxy)silane (403.58 mg, 0.841 mmol, 2.5 equiv.) and 4-amino-1-butanol (30.00 mg, 0.336 mmol, 1.0 equiv.) according to general procedure I. The crude product was purified twice by flash column chromatography according to purification methods A and B to give the pure product as a colorless oil (97 mg, 0.109 mmol, 32% yield). 1 H NMR (500 MHz, benzene-d6) δ 4.88 (m, 2H), δ3.79-3.73 (m, 2H), δ 3.64 (t, 2H), δ 3.42-3.35 (m, 2H), δ2.40-2.36 (m, 4H), δ 2.31-2.28 (m, 2H), δ 1.89-1.22 (m, 68H), δ0.93-087 (m, 12H), δ 0.75-0.71 (m, 4H), δ 0.25 (d, 12H); TOF MS ES + [M+H + ]:886.8121 m / z Example 114 Synthesis of 15-heptyl-5-(10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silanonadecyl)-13,13-dimethyl-12,14,16-trioxa-5-aza-13-silatetracosan-1-ol [ka]

[0201] 15-Heptyl-5-(10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silanonadecyl)-13,13-dimethyl-12,14,16-trioxa-5-aza-13-silatetracosan-1-ol was prepared from 1-bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silanonadecane (416.72 mg, 0.841 mmol, 2.5 equiv.) and 4-amino-1-butanol (29.98 mg, 0.336 mmol, 1.0 equiv.) according to general procedure I. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (169 mg, 0.184 mmol, 55% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.00 (m, 2H), δ3.91-3.82 (m, 2H), δ 3.76 (t, 4H), δ 3.62 (t, 2H), δ 3.46-3.38 (m, 2H), δ 2.33 (t, 4H), δ 2.26 (t, 2H), δ 1.96-1.76 (m, 4H), δ 1.71-1.16 (m, 64H), δ 0.95-0.85 (m, 12H), δ 0.28 (d, 12H); + [M+H + ]:918.7974 m / z Example 115 Synthesis of 15-heptyl-5-(10-heptyl-8,8-dimethyl-7,9-dioxa-11-thia-8-silanonadecyl)-13,13-dimethyl-12,14-dioxa-16-thia-5-aza-13-silatetracosan-1-ol [ka]

[0202] 15-Heptyl-5-(10-heptyl-8,8-dimethyl-7,9-dioxa-11-thia-8-silanonadecyl)-13,13-dimethyl-12,14-dioxa-16-thia-5-aza-13-silatetracosan-1-ol was prepared from 1-bromo-10-heptyl-8,8-dimethyl-7,9-dioxa-11-thia-8-silanonadecane (555.14 mg, 1.085 mmol, 2.5 equiv.) and 4-amino-1-butanol (38.68 mg, 0.4339 mmol, 1.0 equiv.) according to general procedure I. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (170 mg, 0.179 mmol, 41% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.12 (m, 2H), δ3.83-3.75 (m, 4H), δ 3.64-3.61 (t, 2H), δ 2.81-2.66 (m, 4H), δ 2.34 (t, 4H), δ 2.26 (t, TOF MS ES + [M+H + ]:950.7537 m / z Example 116 Synthesis of 6-((dimethyl(octyl)silyl)oxy)-N-(6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)-N-(2-(1-methylpyrrolidin-2-yl)ethyl)-6-(octyloxy)hexan-1-amine [ka]

[0203] 6-((dimethyl(octyl)silyl)oxy)-N-(6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)-N-(2-(1-methylpyrrolidin-2-yl)ethyl)-6-(octyloxy)hexan-1-amine was prepared from ((6-bromo-1(octyloxy)hexyl)oxy)dimethyl(octyl)silane (233.81 mg, 0.487 mmol, 2.5 equiv.) and 2-(2-aminoethyl)-1-methylpyrrolidine (25.00 mg, 0.195 mmol, 1.0 equiv.) according to general procedure O. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (98 mg, 0.106 mmol, 54% yield). 1 H NMR (500 MHz, benzene-d6) δ 4.89 (t, 2H), δ3.78-3.73 (m, 2H), δ 3.41-3.35 (m, 2H), δ 3.01 (dt, 1H), δ2.53-2.36 (m, 6H), δ 2.27 (s, TOF MS ES + [M+H + ]:925.8552 m / z Example 117 Synthesis of 6-((dimethyl(octyloxy)silyl)oxy)-N-(6-((dimethyl(octyloxy)silyl)oxy)-6-(octyloxy)hexyl)-N-(2-(1-methylpyrrolidin-2-yl)ethyl)-6-(octyloxy)hexan-1-amine [ka]

[0204] 6-((dimethyl(octyloxy)silyl)oxy)-N-(6-((dimethyl(octyloxy)silyl)oxy)-6-(octyloxy)hexyl)-N-(2-(1-methylpyrrolidin-2-yl)ethyl)-6-(octyloxy)hexan-1-amine was prepared from 12-(5-bromopentyl)-10,10-dimethyl-9,11,13-trioxa-10-silahenicosane (386.58 mg, 0.780 mmol, 2.5 equiv.) and 2-(2-aminoethyl)-1-methylpyrrolidine (40.00 mg, 0.312 mmol, 1.0 equiv.) according to general procedure O. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (33 mg, 0.034 mmol, 11% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.01 (t, 2H), δ3.90-3.83 (m, 2H), δ 3.77 (t, 4H), δ 3.46-3.36 (m, 2H), δ 3.00 (dt, 1H), δ2.53-2.36 (m, TOF MS ES + [M fragment +H + ]:845.7217 m / z Example 118 Synthesis of N-(2-(1-methylpyrrolidin-2-yl)ethyl)-6-(octyloxy)-N-(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)hexyl)-6-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)hexan-1-amine [ka]

[0205] N-(2-(1-Methylpyrrolidin-2-yl)ethyl)-6-(octyloxy)-N-(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)hexyl)-6-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)hexan-1-amine was prepared from 1-((6-bromo-1(octyloxy)hexyl)oxy)-1,1,3,3-tetramethyl-3-octyldisiloxane (431.93 mg, 0.780 mmol, 2.5 equiv) and 2-(2-aminoethyl)-1-methylpyrrolidine (40.00 mg, 0.312 mmol, 1.0 equiv) according to general procedure O. The crude product was purified twice by flash column chromatography according to purification methods A and B to give the pure product as a colorless oil (71 mg, 0.066 mmol, 21% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.02 (t, 2H), δ3.90-3.84 (m, 2H), δ 3.46-3.30 (m, 2H), δ 3.00 (dt, 1H), δ2.53-2.38 (m, 6H), δ 2.29 (s, TOF MS ES + [M fragment +H + ]:518.4431 m / z Example 119 Synthesis of N-(2-(1-methylpyrrolidin-2-yl)ethyl)-6-(octyloxy)-N-(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)hexyl)-6-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)hexan-1-amine [ka]

[0206] N-(2-(1-Methylpyrrolidin-2-yl)ethyl)-6-(octyloxy)-N-(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)hexyl)-6-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)hexan-1-amine was prepared from 1-((6-bromo-1(octyloxy)hexyl)oxy)-1,1,3,3-tetramethyl-3-(octyloxy)disiloxane (444.41 mg, 0.780 mmol, 2.5 equiv) and 2-(2-aminoethyl)-1-methylpyrrolidine (40.00 mg, 0.312 mmol, 1.0 equiv) according to general procedure O. The crude product was purified twice by flash column chromatography according to purification methods A and B to give the pure product as a colorless oil (92 mg, 0.083 mmol, 27% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.04 (t, 2H), δ3.91-3.85 (m, 2H), δ 3.76 (t, 4H), δ 3.47-3.36 (m, 2H), δ 3.00 (dt, 1H), δ 2.53-2.38 (m, TOF MS ES + [M fragment +H + ]:603.4640 m / z Example 120 Synthesis of 6-((1-((dimethyl(octyl)silyl)oxy)octyl)oxy)-N-(6-((1-((dimethyl(octyl)silyl)oxy)octyl)oxy)hexyl)-N-(2-(1-methylpyrrolidin-2-yl)ethyl)hexan-1-amine [ka]

[0207] 6-((1-((dimethyl(octyl)silyl)oxy)octyl)oxy)-N-(6-((1-((dimethyl(octyl)silyl)oxy)octyl)oxy)hexyl)-N-(2-(1-methylpyrrolidin-2-yl)ethyl)hexan-1-amine was prepared from ((1-((6-bromohexyl)oxy)octyl)oxy)dimethyl(octyl)silane (374.1 mg, 0.780 mmol, 2.5 equiv.) and 2-(2-aminoethyl)-1-methylpyrrolidine (40.00 mg, 0.312 mmol, 1.0 equiv.) according to general procedure O. The crude product was purified twice by flash column chromatography according to purification methods A and B to give the pure product as a colorless oil (109 mg, 0.118 mmol, 38% yield). 1 H NMR (500 MHz, benzene-d6) δ 4.88 (t, 2H), δ3.79-3.73 (m, 2H), δ 3.41-3.35 (m, 2H), δ 3.00 (dt, 1H), δ2.53-2.36 (m, 6H), δ 2.29 (s, 3H), δ 2.12-1.19 (m, 72H), δ0.95-0.89 (m, 12H), δ 0.75-0.71 (4H), δ 0.25 (d, 12H) Example 121 Synthesis of 8-heptyl-N-(8-heptyl-10,10-dimethyl-7,9,11-trioxa-10-silanonadecyl)-10,10-dimethyl-N-(2-(1-methylpyrrolidin-2-yl)ethyl)-7,9,11-trioxa-10-silanonadecan-1-amine [ka]

[0208] 8-Heptyl-N-(8-heptyl-10,10-dimethyl-7,9,11-trioxa-10-silanonadecyl)-10,10-dimethyl-N-(2-(1-methylpyrrolidin-2-yl)ethyl)-7,9,11-trioxa-10-silanonadecan-1-amine was prepared from 1-bromo-8-heptyl-10,10-dimethyl-7,9,11-trioxa-10-silanonadecane (386.58 mg, 0.780 mmol, 2.5 equiv) and 2-(2-aminoethyl)-1-methylpyrrolidine (40.00 mg, 0.312 mmol, 1.0 equiv) according to general procedure O. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (60 mg, 0.063 mmol, 20% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.01 (t, 2H), δ3.90-3.84 (m, 2H), δ 3.77 (t, 4H), δ 3.46-3.40 (m, 2H), δ 3.00 (dt, 1H), δ 2.53-2.37 (m, 6H), δ 2.29 (s, 3H), δ 2.10-1.17 (m, 72H), δ0.93-0.89 (m, 12H), δ 0.29 (d, 12H) Example 122 Synthesis of N-(2-(1-methylpyrrolidin-2-yl)ethyl)-6-((1-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)octyl)oxy)-N-(6-((1-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)octyl)oxy)hexyl)hexan-1-amine [ka]

[0209] N-(2-(1-Methylpyrrolidin-2-yl)ethyl)-6-((1-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)octyl)oxy)-N-(6-((1-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)octyl)oxy)hexyl)hexan-1-amine was prepared from 1-((1-((6-bromohexyl)oxy)octyl)oxy)-1,1,3,3-tetramethyl-3-octyldisiloxane (431.93 mg, 0.780 mmol, 2.5 equiv) and 2-(2-aminoethyl)-1-methylpyrrolidine (40.00 mg, 0.312 mmol, 1.0 equiv) according to general procedure O. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (200 mg, 0.186 mmol, 60% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.01 (t, 2H), δ3.91-3.83 (m, 2H), δ 3.45-3.37 (m, 2H), δ 2.99 (dt, 1H), δ2.52-2.36 (m, 6H), δ 2.28 (s, 3H), δ 2.10-1.20 (m, 72H), δ0.95-0.89 (m, 12H), δ 0.69-0.65 (m, 4H), δ 0.26 (d, 12H), δ 0.20 (s, 12H) Example 123 Synthesis of N-(2-(1-methylpyrrolidin-2-yl)ethyl)-6-((1-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)octyl)oxy)-N-(6-((1-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)octyl)oxy)hexyl)hexan-1-amine [ka]

[0210] N-(2-(1-methylpyrrolidin-2-yl)ethyl)-6-((1-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)octyl)oxy)-N-(6-((1-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)octyl)oxy)hexyl)hexan-1-amine was prepared from 1-((1-((6-bromohexyl)oxy)octyl)oxy)-1,1,3,3-tetramethyl-3-(octyloxy)disiloxane (444.41 mg, 0.780 mmol, 2.5 equiv) and 2-(2-aminoethyl)-1-methylpyrrolidine (40.00 mg, 0.312 mmol, 1.0 equiv) according to general procedure O. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (100 mg, 0.090 mmol, 29% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.03 (t, 2H), δ3.93-3.83 (m, 2H), δ 3.76 (t, 4H), δ 3.46-3.35 (m, 2H), δ 3.00 (dt, 1H), δ 2.54-2.35 (m, 6H), δ 2.28 (s, 3H), δ 2.10-1.17 (m, 72H), δ0.94-0.86 (m, 12H), δ 0.32 (d, 12H), δ 0.27 (s, 12H) Example 124 Synthesis of 2-(4-((bis(6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)amino)methyl)-1H-1,2,3-triazol-1-yl)ethan-1-ol [ka]

[0211] 2-(4-((bis(6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)amino)methyl)-1H-1,2,3-triazol-1-yl)ethan-1-ol was prepared from 6-((dimethyl(octyl)silyl)oxy)-N-(6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)-6-(octyloxy)-N-(prop-2-yn-1-yl)hexan-1-amine (130.00 mg, 0.152 mmol, 1.0 equiv) and 2-azidoethanol (39.84 mg (50%), 0.229 mmol, 1.5 equiv). The crude product was purified twice by flash column chromatography according to purification methods A and B to give the pure product as a colorless oil (63 mg, 0.067 mmol, 44% yield). 1 H NMR (500 MHz, CDCl3) δ 4.69 (t, 2H), δ 4.48-4.45 (m, 2H), δ 4.04-4.02 (m, 2H), δ 3.78 (s, 2H), δ3.63-3.57 (m, 2H), δ 3.31-3.25 (m, 2H), δ 4.45 (t, 4H), δ1.62-1.42 (m, 12H), δ 1.41-1.18 (m, 53H), δ 0.89-0.86 (m, 12H), δ0.62-0.58 (m, 4H), δ 0.12 (d, 12H); TOF MS ES + [M+H + ]:940.554 m / z Example 125 Synthesis of (3R,4R,5S,6R)-3-(4-((bis(6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)amino)methyl)-1H-1,2,3-triazol-1-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-2,4,5-triol [ka]

[0212] (3R,4R,5S,6R)-3-(4-((bis(6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)amino)methyl)-1H-1,2,3-triazol-1-yl)-6-(hydroxymethyl)tetrahydro-2H-pyran-2,4,5-triol was prepared from 6-((dimethyl(octyl)silyl)oxy)-N-(6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)-6-(octyloxy)-N-(prop-2-yn-1-yl)hexan-1-amine (130.00 mg, 0.152 mmol, 1.0 equiv) and 2-azido-2-deoxy-D-glucose (46.93 mg, 0.229 mmol, 1.5 equiv) according to General Procedure P. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (89 mg, 0.084 mmol, 55% yield). 1 H NMR (500 MHz, CDCl3) δ 7.83 (s, 1H), δ 7.63 (s, 1H), δ 5.35 (s, 1H), δ 5.08 (d, 1H), δ 4.67 (t, 2H), δ 4.34-4.13 (m, 2H), δ 4.01 (d, 1H), δ 3.95-3.75 (m, 2H), δ3.74-3.46 (br. m, 6H), δ 3.30-3.25 (q, 2H), δ 2.42-2.39 (br. m, 4H), δ 2.23 (m, 1H), δ 1.64-1.11 (m, 64H), δ 0.87 (m, 12H), δ 0.60 (m, 4H), δ 0.11 (d, 12H); LC ESI MS [M+H + ]:1057.843 m / z Example 126 Synthesis of N-((2R,3R,4R,5S,6R)-2-(4-((bis(6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)amino)methyl)-1H-1,2,3-triazol-1-yl)-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)acetamide [ka]

[0213] N-((2R,3R,4R,5S,6R)-2-(4-((bis(6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)amino)methyl)-1H-1,2,3-triazol-1-yl)-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)acetamide was prepared by 6-((dimethyl(octyl)silyl) )oxy)-N-(6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)-6-(octyloxy)-N-(prop-2-yn-1-yl)hexan-1-amine (100.00 mg, 0.117 mmol, 1.0 equiv.) and 2-acetamido-2-deoxy-β-D-glucopyranosyl azide (43.32 mg, 0.176 mmol, 1.5 equiv.). The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (88 mg, 0.080 mmol, 68% yield). 1 H NMR (500 MHz, CDCl3) δ 7.89 (s, 1H), δ 6.95 (s, 1H), δ 5.91 (d, 1H), δ 5.30-4.87 (s, 2H), δ4.71-4.68 (m, 2H), δ 4.37-4.30 (m, 1H), δ 3.95-3.87 (m, 4H), δ3.74-3.57 (m, 5H), δ 3.31-3.26 (m, 2H), δ 2.47-2.40 (m, 4H), δ 1.75 (s, 3H), δ 1.63-1.41 (m, 12H), δ 1.38-1.20 (m, 53H), δ 0.89-0.86 (m, 12H), δ0.62-0.58 (m, 4H), δ 0.12 (d, 12H); LC ESI MS [M+H + ]:1098.624 m / z Example 127 Synthesis of N-((2R,3R,4R,5S,6R)-2-(4-((bis(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)hexyl)amino)methyl)-1H-1,2,3-triazol-1-yl)-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)acetamide [ka]

[0214] N-((2R,3R,4R,5S,6R)-2-(4-((bis(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)hexyl)amino)methyl)-1H-1,2,3-triazol-1-yl)-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)acetamide was prepared according to general procedure P from 6-(octyloxy)-N-(6-(octyloxy) )-6-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)hexyl)-N-(prop-2-yn-1-yl)-6-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)hexan-1-amine (83.00 mg, 0.083 mmol, 1.0 equiv.) and 2-acetamido-2-deoxy-β-D-glucopyranosyl azide (30.63 mg, 0.124 mmol, 1.5 equiv.). The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (30 mg, 0.024 mmol, 29% yield). 1H NMR (500 MHz, CDCl3) δ 8.04 (s, 1H), δ 7.21 (s, 1H), δ 5.89 (d, 1H), δ 4.77 (t, 2H), δ4.39-4.36 (m, 1H), δ 4.14-3.83 (m, 6H), δ 3.69-3.65 (m, 3H), δ3.31-3.25 (m, 2H), δ 2.90-2.26 (m, 6H), δ 1.75 (s, 3H), δ1.65-1.45 (m, 12H), δ 1.43-1.13 (m, 53H), δ 0.89-0.85 (m, 12H), δ 0.55-0.51 (m, 4H), δ 0.11 (d, 12H), δ 0.09 (s, 12H); ); LC ESI MS [M+H + ]:1247.980 m / z Example 128 Synthesis of 6-((6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)(4-hydroxybutyl)amino)hexyl 2-hexyldecanoate [ka]

[0215] 6-((6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)(4-hydroxybutyl)amino)hexyl 2-hexyldecanoate was prepared from 4-((6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)amino)butan-1-ol (150 mg, 0.307 mmol, 1.0 equiv.) and 6-oxohexyl 2-hexyldecanoate (109.01 mg, 0.307 mmol, 1.0 equiv.) according to general procedure J. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (90 mg, 0.109 mmol, 35% yield). 1H NMR (500 MHz, benzene-d6) δ 4.90 (t, 1H), δ 4.12 (t, 2H), δ 3.80-3.74 (m, 1H), δ 3.62 (t, 2H), δ 3.42-3.34 (m, 2H), δ 2.48 (m, 1H), TOF MS ES + [M+H + ]:826.7701 m / z Example 129 Synthesis of 15-heptyl-7-(4-hydroxybutyl)-17,17-dimethyl-14,16-dioxa-7-aza-17-silapentacosyl 2-hexyldecanoate [ka]

[0216] 15-Heptyl-7-(4-hydroxybutyl)-17,17-dimethyl-14,16-dioxa-7-aza-17-silapentacosyl 2-hexyldecanoate was prepared from 13-heptyl-15,15-dimethyl-12,14-dioxa-5-aza-15-silatricosan-1-ol (150 mg, 0.307 mmol, 1.0 equiv.) and 6-oxohexyl 2-hexyldecanoate (109.01 mg, 0.307 mmol, 1.0 equiv.) according to general procedure J. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (38 mg, 0.046 mmol, 15% yield). 1H NMR (500 MHz, benzene-d6) δ 4.88 (t, 1H), δ 4.11 (t, 2H), δ 3.78-3.73 (m, 1H), δ 3.62 (t, 2H), δ 3.40-3.35 (m, 1H), δ2.47(m, 2H), TOF MS ES + [M+H + ]:826.7683 m / z Example 130 Synthesis of 7-(4-hydroxybutyl)-15,15-dimethyl-13-(octyloxy)-14,16-dioxa-7-aza-15-silatetracosyl 2-hexyldecanoate [ka]

[0217] 7-(4-Hydroxybutyl)-15,15-dimethyl-13-(octyloxy)-14,16-dioxa-7-aza-15-silatetracosyl 2-hexyldecanoate was prepared from 12-(5-bromopentyl)-10,10-dimethyl-9,11,13-trioxa-10-silahenicosane (191.21 mg, 0.386 mmol, 1.1 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (150 mg, 0.351 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (150 mg, 0.178 mmol, 51% yield). 1H NMR (500 MHz, benzene-d6) δ 5.01 (t, 1H), δ 4.12 (t, 2H), δ3.90-3.84 (m, 1H), δ 3.77 (t, 2H), δ 3.62 (t, 2H), δ3.46-3.34 (m, 2H), δ 2.50-2.43 (m, 1H), δ 2.35-2.21 (m, 6H), δ1.95-1.71 (m, 4H), δ 1.69-1.12 (m, 63H), δ 0.93-0.88 (m, 12H), δ 0.29 (d, 6H); TOF MS E.S. + [M+H + ]:842.7618 m / z Example 131 Synthesis of 15-heptyl-7-(4-hydroxybutyl)-17,17-dimethyl-14,16,18-trioxa-7-aza-17-silahexacosyl 2-hexyldecanoate [ka]

[0218] 15-Heptyl-7-(4-hydroxybutyl)-17,17-dimethyl-14,16,18-trioxa-7-aza-17-silahexacosyl 2-hexyldecanoate was prepared from 1-bromo-8-heptyl-10,10-dimethyl-7,9,11-trioxa-10-silanonadecane (173.83 mg, 0.351 mmol, 1.0 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (150.00 mg, 0.351 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (153 mg, 0.182 mmol, 52% yield). 1H NMR (500 MHz, benzene-d6) δ 5.00 (t, 1H), δ 4.11 (t, 2H), δ3.92-3.83 (m, 1H), δ 3.76 (t, 2H), δ 3.62 (t, 2H), δ3.44-3.40 (m, 2H), δ 2.47 (m, 1H), δ 2.34-2.23 (m, 6H), δ1.95-1.73 (m, 4H), δ 1.69-1.12 (m, 63H), δ 0.93-0.88 (m, 12H), δ 0.29 (d, 6H); TOF MS ES + [M+H + ]:842.7665 m / z Example 132 Synthesis of 6-((4-hydroxybutyl)(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)hexyl)amino)hexyl 2-hexyldecanoate [ka]

[0219] 6-((4-Hydroxybutyl)(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)hexyl)amino)hexyl 2-hexyldecanoate was prepared from 1-((6-bromo-1-(octyloxy)hexyl)oxy)-1,1,3,3-tetramethyl-3-octyldisiloxane (168.33 mg, 0.304 mmol, 1.0 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (130 mg, 0.304 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (142 mg, 0.158 mmol, 52% yield). 1H NMR (500 MHz, benzene-d6) δ 5.01 (t, 1H), δ 4.12 (t, 2H), δ 3.92-3.83 (m, 1H), δ 3.62 (t, 2H), δ 3.47-3.39 (m, 1H), δ 2.47 (m, 1H), TOF MS ES + [M+H + ]:900.7888 m / z Example 133 Synthesis of 15-heptyl-7-(4-hydroxybutyl)-17,17,19,19-tetramethyl-14,16,18-trioxa-7-aza-17,19-disilaheptacosyl 2-hexyldecanoate [ka]

[0220] 15-Heptyl-7-(4-hydroxybutyl)-17,17,19,19-tetramethyl-14,16,18-trioxa-7-aza-17,19-disilaheptacosyl 2-hexyldecanoate was prepared from 1-((1-((6-bromohexyl)oxy)octyl)oxy)-1,1,3,3-tetramethyl-3-octyldisiloxane (194.22 mg, 0.351 mmol, 1.0 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (150 mg, 0.351 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (169 mg, 0.188 mmol, 54% yield). 1H NMR (500 MHz, benzene-d6) δ 5.01 (t, 1H), δ 4.11 (t, 2H), δ 3.93-3.85 (m, 1H), δ 3.62 (t, 2H), δ 3.45-3.38 (m, 1H), δ 2.47 (m, 1H), TOF MS ES + [M+H + ]:900.7840 m / z Example 134 Synthesis of 6-((4-hydroxybutyl)(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)hexyl)amino)hexyl 2-hexyldecanoate [ka]

[0221] 6-((4-Hydroxybutyl)(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)hexyl)amino)hexyl 2-hexyldecanoate was prepared from 4-((6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)hexyl)amino)butan-1-ol (126 mg, 0.218 mmol, 1.0 equiv.) and 6-oxohexyl 2-hexyldecanoate (77.29 mg, 0.218 mmol, 1.0 equiv.) according to general procedure J. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (53 mg, 0.058 mmol, 27% yield). 1H NMR (500 MHz, benzene-d6) δ 5.03 (t, 1H), δ 4.11 (t, 2H), δ 3.91-3.85 (m, 1H), δ 3.76 (t, 2H), δ 3.61 (t, 2H), δ 3.46-3.41 (m, 1H), TOF MS ES + [M+H + ]:916.7822 m / z Example 135 Synthesis of 15-heptyl-7-(4-hydroxybutyl)-17,17,19,19-tetramethyl-14,16,18,20-tetraoxa-7-aza-17,19-disilaoctacosyl 2-hexyldecanoate [ka]

[0222] 15-Heptyl-7-(4-hydroxybutyl)-17,17,19,19-tetramethyl-14,16,18,20-tetraoxa-7-aza-17,19-disilaoctacosyl 2-hexyldecanoate was prepared from 1-((1-((6-bromohexyl)oxy)octyl)oxy)-1,1,3,3-tetramethyl-3-(octyloxy)disiloxane (190.51 mg, 0.334 mmol, 1.1 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (130 mg, 0.304 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (51 mg, 0.056 mmol, 18% yield). 1H NMR (500 MHz, benzene-d6) δ 5.04 (t, 1H), δ 4.12 (t, 2H), δ 3.91-3.85 (m, 1H), δ 3.76 (t, 2H), δ 3.62 (t, 2H), δ 3.47-3.36 (m, 1H), TOF MS ES + [M+H + ]:916.7834 m / z Example 136 Synthesis of 18-hexyl-7-(4-hydroxybutyl)-15,15-dimethyl-13-(octyloxy)-14,16-dioxa-7-aza-15-silahexacosyl 2-hexyldecanoate [ka]

[0223] 18-Hexyl-7-(4-hydroxybutyl)-15,15-dimethyl-13-(octyloxy)-14,16-dioxa-7-aza-15-silahexacosyl 2-hexyldecanoate was prepared from 10-(5-bromopentyl)-15-hexyl-12,12-dimethyl-9,11,13-trioxa-12-silatricosane (234.50 mg, 0.386 mmol, 1.1 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (150 mg, 0.351 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (179 mg, 0.188 mmol, 53% yield). 1H NMR (500 MHz, benzene-d6) δ 5.03 (t, 1H), δ 4.12 (t, 2H), δ 3.92-3.86 (m, 1H), δ 3.75 (d, 2H), δ 3.62 (t, 2H), δ3.48-3.42 (m, 1H), TOF MS ES + [M+H + ]:954.8895 m / z Example 137 Synthesis of 15-heptyl-20-hexyl-7-(4-hydroxybutyl)-17,17-dimethyl-14,16,18-trioxa-7-aza-17-silaoctacosyl 2-hexyldecanoate [ka]

[0224] 15-Heptyl-20-hexyl-7-(4-hydroxybutyl)-17,17-dimethyl-14,16,18-trioxa-7-aza-17-silaoctacosyl 2-hexyldecanoate was prepared from 1-bromo-8-heptyl-13-hexyl-10,10-dimethyl-7,9,11-trioxa-10-silahenicosane (234.50 mg, 0.386 mmol, 1.1 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (150 mg, 0.351 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (210 mg, 0.220 mmol, 63% yield). 1H NMR (500 MHz, benzene-d6) δ 5.03 (t, 1H), δ 4.12 (t, 2H), δ 3.91-3.85 (m, 1H), δ 3.75 (d, 2H), δ 3.62 (t, 2H), δ3.46-3.40 (m, 1H), δ 2.50-2.43 (m, 1H), δ 2.34-2.24 (m, 6H), δ 1.97-1.12 (m, 81H), δ 0.96-0.87 (m, 12H), δ 0.30 (d, 6H); + [M+H + ]:954.8887 m / z Example 138 Synthesis of 16-heptyl-7-(4-hydroxybutyl)-14,14-dimethyl-15,17-dioxa-7-aza-14-silapentacosyl 2-hexyldecanoate [ka]

[0225] 16-Heptyl-7-(4-hydroxybutyl)-14,14-dimethyl-15,17-dioxa-7-aza-14-silapentacosyl 2-hexyldecanoate was prepared from (6-bromohexyl)dimethyl((1-(octyloxy)octyl)oxy)silane (185.04 mg, 0.386 mmol, 1.1 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (150 mg, 0.351 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (197 mg, 0.238 mmol, 68% yield). 1H NMR (500 MHz, benzene-d6) δ 4.88 (dt, 1H), δ 4.12 (t, 2H), δ 3.79-3.73 (m, 1H), δ 3.63 (t, 2H), δ 3.41-3.35 (m, 1H), δ2.54-2.42 (m, TOF MS ES + [M+H + ]:826.7684 m / z Example 139 Synthesis of 17-heptyl-7-(4-hydroxybutyl)-15,15-dimethyl-14,16,18-trioxa-7-aza-15-silahexacosyl 2-hexyldecanoate [ka]

[0226] 17-Heptyl-7-(4-hydroxybutyl)-15,15-dimethyl-14,16,18-trioxa-7-aza-15-silahexacosyl 2-hexyldecanoate was prepared from 1-bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silanonadecane (191.21 mg, 0.386 mmol, 1.1 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (150 mg, 0.351 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (94 mg, 0.112 mmol, 32% yield). 1H NMR (500 MHz, benzene-d6) δ 5.00 (t, 1H), δ 4.12 (t, 2H), δ 3.89-3.84 (m, 1H), δ 3.77 (t, 2H), δ 3.62 (t, 2H), δ3.45-3.37 (m, 1H), δ 2.50-2.43 (m, 1H), δ 2.34-2.24 (m, 6H), δ 1.95-1.12 (m, 68H), δ 0.95-0.86 (m, 12H), δ 0.28 (d, 6H); + [M+H + ]:842.7627 m / z Example 140 Synthesis of 17-heptyl-7-(4-hydroxybutyl)-15,15-dimethyl-14,16,18-trioxa-7-aza-15-silapentacosyl 2-hexyldecanoate [ka]

[0227] 17-Heptyl-7-(4-hydroxybutyl)-15,15-dimethyl-14,16,18-trioxa-7-aza-15-silapentacosyl 2-hexyldecanoate was prepared from 1-bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silaoctadecane (522.56 mg, 1.122 mmol, 1.2 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (400 mg, 0.935 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (355 mg, 0.428 mmol, 46% yield). 1H NMR (500 MHz, benzene-d6) δ 4.96 (t, 1H), δ 4.09 (t, 2H), δ 3.85-3.80 (m, 1H), δ 3.74 (t, 2H), δ 3.61 (t, 2H), δ3.41-3.36 (m, 1H), δ 2.47-2.40 (m, 1H), δ 2.32-2.25 (m, 6H), δ1.91-1.15 (m, 66H), δ 0.92-0.87 (m, 12H), δ 0.25 (d, 6H); + [M+H + ]:828.7474 m / z Example 141 Synthesis of 17-heptyl-7-(4-hydroxybutyl)-15,15-dimethyl-14,16,18-trioxa-7-aza-15-silaheptacosyl 2-hexyldecanoate [ka]

[0228] 17-Heptyl-7-(4-hydroxybutyl)-15,15-dimethyl-14,16,18-trioxa-7-aza-15-silaheptacosyl 2-hexyldecanoate was prepared from 1-bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silaycosane (326.04 mg, 0.640 mmol, 1.2 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (228 mg, 0.533 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (144 mg, 0.168 mmol, 32% yield). 1H NMR (500 MHz, benzene-d6) δ 5.01 (t, 1H), δ 4.12 (t, 2H), δ 3.91-3.83 (m, 1H), δ 3.77 (t, 2H), δ 3.62 (t, 2H), δ3.47-3.36 (m, 1H), TOF MS ES + [M+H + ]:856.7791 m / z Example 142 Synthesis of 17-hexyl-7-(4-hydroxybutyl)-15,15-dimethyl-14,16,18-trioxa-7-aza-15-silahexacosyl 2-hexyldecanoate [ka]

[0229] 17-Hexyl-7-(4-hydroxybutyl)-15,15-dimethyl-14,16,18-trioxa-7-aza-15-silahexacosyl 2-hexyldecanoate was prepared from 1-bromo-10-hexyl-8,8-dimethyl-7,9,11-trioxa-8-silanonadecane (522.56 mg, 1.122 mmol, 1.2 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (400.0 mg, 0.935 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (385 mg, 0.465 mmol, 50% yield). 1H NMR (500 MHz, benzene-d6) δ 5.00 (t, 1H), δ 4.12 (t, 2H), δ 3.93-3.82 (m, 1H), δ 3.77 (t, 2H), δ 3.62 (t, 2H), δ3.45-3.37 (m, 1H), TOF MS ES + [M+H + ]:828.7489 m / z Example 143 Synthesis of 7-(4-hydroxybutyl)-15,15-dimethyl-17-octyl-14,16,18-trioxa-7-aza-15-silahexacosyl 2-hexyldecanoate [ka]

[0230] 7-(4-Hydroxybutyl)-15,15-dimethyl-17-octyl-14,16,18-trioxa-7-aza-15-silahexacosyl 2-hexyldecanoate was prepared from 1-bromo-8,8-dimethyl-10-octyl-7,9,11-trioxa-8-silanonadecane (554.04 mg, 1.122 mmol, 1.2 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (400 mg, 0.935 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (398 mg, 0.465 mmol, 50% yield). 1H NMR (500 MHz, CDCl3) δ 5.11 (t, 1H), δ 4.22 (t, 2H), δ 4.00-3.93 (m, 1H), δ 3.88 (t, 2H), δ 3.72 (t, 2H), δ 3.56-3.45 (m, 1H), δ 2.60-2.51 (m, 1H), δ 2.45-2.34 (m, 6H), δ2.05-1.21 (br. m, 70H), δ 1.04-0.98 (m, 12H) δ 0.39 (d, 6H); TOF MS ES + [M+H + ]:856.7808 m / z Example 144 Synthesis of 18-(4-hydroxybutyl)-10,10-dimethyl-8-nonyl-7,9,11-trioxa-18-aza-10-silatetracosan-24-yl 2-hexyldecanoate [ka]

[0231] 18-(4-Hydroxybutyl)-10,10-dimethyl-8-nonyl-7,9,11-trioxa-18-aza-10-silatetracosan-24-yl 2-hexyldecanoate was prepared from 1-bromo-8,8-dimethyl-10-nonyl-7,9,11-trioxa-8-silaheptadecane (556.25 mg, 1.122 mmol, 1.2 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (400 mg, 0.9352 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (344 mg, 0.408 mmol, 44% yield). H NMR (500 MHz, benzene-d6) δ 5.00 (t, 1H), δ 4.12 (t, 2H), δ 3.88-3.82 (m, 1H), δ 3.77 (t, 2H), δ 3.62 (t, 2H), δ 3.44-3.38 (m, 1H), TOF MS ES + [M+H + ]:842.7653 m / z Example 145 Synthesis of 7-(4-hydroxybutyl)-15,15-dimethyl-17-pentyl-14,16,18-trioxa-7-aza-15-silaoctacosyl 2-hexyldecanoate [ka]

[0232] 7-(4-Hydroxybutyl)-15,15-dimethyl-17-pentyl-14,16,18-trioxa-7-aza-15-silaoctacosyl 2-hexyldecanoate was prepared from 1-bromo-8,8-dimethyl-10-pentyl-7,9,11-trioxa-8-silahenicosane (556.25 mg, 1.122 mmol, 1.2 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (400 mg, 0.935 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (375 mg, 0.445 mmol, 48% yield). H NMR (500 MHz, benzene-d6) δ 4.97 (t, 1H), δ 4.10 (t, 2H), δ 3.87-3.82 (m, 1H), δ 3.75 (t, 2H), δ 3.61 (t, 2H), δ 3.42-3.38 (m, 1H), TOF MS ES + [M+H + ]:842.7642 m / z Example 146 Synthesis of 16-heptyl-7-(4-hydroxybutyl)-14,14-dimethyl-13,15,17-trioxa-7-aza-14-silapentacosyl 2-hexyldecanoate [ka]

[0233] 16-Heptyl-7-(4-hydroxybutyl)-14,14-dimethyl-13,15,17-trioxa-7-aza-14-silapentacosyl 2-hexyldecanoate was prepared from 1-bromo-9-heptyl-7,7-dimethyl-6,8,10-trioxa-7-silaoctadecane (270.26 mg, 0.561 mmol, 1.2 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (200 mg, 0.468 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (150 mg, 0.181 mmol, 39% yield). H NMR (500 MHz, benzene-d6) δ 5.01 (t, 1H), δ 4.12 (t, 2H), δ 3.90-3.83 (m, 1H), δ 3.78 (t, 2H), δ 3.62 (t, 2H), δ 3.47-3.39 (m, 1H), δ 3.36 (t, 2H), δ 2.34-2.24 (m, 6H), δ1.96-1.08 (br. m, 66H), δ 0.94-0.88 (m, 12H) δ 0.29 (d, 6H); LC ESI MS[M+H + ]:828.860 m / z Example 147 Synthesis of 17-heptyl-7-(4-hydroxybutyl)-15,15-dimethyl-14,16-dioxa-18-thia-7-aza-15-silahexacosyl 2-hexyldecanoate [ka]

[0234] 17-Heptyl-7-(4-hydroxybutyl)-15,15-dimethyl-14,16-dioxa-18-thia-7-aza-15-silahexacosyl 2-hexyldecanoate was prepared from 1-bromo-10-heptyl-8,8-dimethyl-7,9-dioxa-11-thia-8-silanonadecane (574.28 mg, 1.122 mmol, 1.2 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (400 mg, 0.935 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (288 mg, 0.330 mmol, 35% yield). H NMR (500 MHz, benzene-d6) δ 5.11 (t, 1H), δ 4.12 (t, 2H), δ 3.83-3.74 (m, 2H), δ 3.62 (t, 2H), δ2.80-2.65 (m, 2H), δ 2.50-2.41 (m, TOF MS ES + [M+H + ]:858.7407 m / z Example 148 Synthesis of 17-heptyl-7-(2-hydroxyethyl)-15,15-dimethyl-14,16,18-trioxa-7-aza-15-silahexacosyl 2-hexyldecanoate [ka]

[0235] 17-Heptyl-7-(2-hydroxyethyl)-15,15-dimethyl-14,16,18-trioxa-7-aza-15-silahexacosyl 2-hexyldecanoate was prepared from 1-bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silanonadecane (654.83 mg, 1.321 mmol, 1.1 equiv.) and 6-((2-hydroxyethyl)amino)hexyl 2-hexyldecanoate (480 mg, 1.201 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (190 mg, 0.233 mmol, 19% yield). 1H NMR (500 MHz, benzene-d6) δ 5.00 (dt, 1H), δ 4.12 (t, 2H), δ 3.91-3.82 (m, 1H), δ 3.77 (t, 2H), δ 3.52 (t, 2H), δ3.46-3.38 (m, 1H), TOF MS ES + [M+H + ]:814.7322 m / z Example 149 Synthesis of 9-heptyl-20-(4-hydroxybutyl)-7,7-dimethyl-8,10-dioxa-20-aza-7-silahexacosan-26-yl 2-hexyldecanoate [ka]

[0236] 9-Heptyl-20-(4-hydroxybutyl)-7,7-dimethyl-8,10-dioxa-20-aza-7-silahexacosan-26-yl 2-hexyldecanoate was prepared from ((1-((9-bromononyl)oxy)octyl)oxy)(hexyl)dimethylsilane (634.84 mg, 1.286 mmol, 1.1 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (500 mg, 1.169 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (439 mg, 0.522 mmol, 45% yield). 1H NMR (500 MHz, benzene-d6) δ 4.89 (dt, 1H), δ 4.12 (t, 2H), δ 3.80-3.74 (m, 1H), δ 3.63 (t, 2H), δ 3.42-3.36 (m, 1H), δ2.49-2.44 (m, TOF MS ES + [M+H + ]:840.7838 m / z Example 150 Synthesis of 17-heptyl-7-(4-hydroxybutyl)-13,13,15,15-tetramethyl-12,14,16,18-tetraoxa-7-aza-13,15-disilahexacosyl 2-hexyldecanoate [ka]

[0237] 17-Heptyl-7-(4-hydroxybutyl)-13,13,15,15-tetramethyl-12,14,16,18-tetraoxa-7-aza-13,15-disilahexacosyl 2-hexyldecanoate was prepared from 1-(4-bromobutoxy)-1,1,3,3-tetramethyl-3-((1-(octyloxy)octyl)oxy)disiloxane (501.6 mg, 0.926 mmol, 1.1 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (360 mg, 0.842 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (194 mg, 0.218 mmol, 26% yield). 1H NMR (500 MHz, benzene-d6) δ 4.69 (t, 1H), δ 3.95 (t, 2H), δ 3.61-3.51 (m, 3H), δ 3.48-3.41 (m, 2H), δ 3.21-3.16 (m, 1H), δ2.41-2.30 (m, 6H), δ 2.23-2.16 (m, 1H), δ 1.64-1.06 (br. m, 64H), δ 0.77 (t, 12H), δ 0.05 (d, 6H), δ 0.00 (s, 6H); LC ESI MS[M+H + ]:888.640 m / z Example 151 Synthesis of 6-((6-((dimethyl((oxacyclohexadecan-2-yl)oxy)silyl)oxy)hexyl)(4-hydroxybutyl)amino)hexyl 2-hexyldecanoate [ka]

[0238] 6-((6-((dimethyl((oxacyclohexadecan-2-yl)oxy)silyl)oxy)hexyl)(4-hydroxybutyl)amino)hexyl 2-hexyldecanoate was prepared from ((6-bromohexyl)oxy)dimethyl((oxacyclohexadecan-2-yl)oxy)silane (911.1 mg, 1.900 mmol, 1.25 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (650 mg, 1.520 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (366 mg, 0.443 mmol, 29% yield). 1H NMR (500 MHz, benzene-d6) δ 4.96-4.93 (dd, 1H), δ 4.12 (t, 2H), δ 3.98-3.90 (m, 1H), δ 3.74 (t, 2H), δ 3.62 (t, 2H), δ2.35-2.27 (m, LC ESI MS[M+H + ]:826.680 m / z Example 152 Synthesis of (Z)-17-heptyl-7-(4-hydroxybutyl)-15,15-dimethyl-14,16,18-trioxa-7-aza-15-silaheptacos-24-en-1-yl 2-hexyldecanoate [ka]

[0239] (Z)-17-heptyl-7-(4-hydroxybutyl)-15,15-dimethyl-14,16,18-trioxa-7-aza-15-silaheptacos-24-en-1-yl 2-hexyldecanoate was prepared from (Z)-1-bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silaicos-17-ene (1.073 g, 2.057 mmol, 1.1 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (800 mg, 1.870 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (200 mg, 0.234 mmol, 12% yield). 1H NMR (500 MHz, benzene-d6) δ 5.48-5.38 (m, 2H), δ 4.98 (dt, 1H), δ 4.12 (t, 2H), δ 3.92-3.81 (m, 1H), δ 3.76 (t, 2H), δ 3.62 (t, 2H), δ 3.42-3.36 (m, 1H), δ 2.50-2.42 (m, 1H), δ 2.37-2.18 (m, 6H), δ2.07-1.97 (m, 4H), δ1.94-1.20 (br. m, 62H), δ 0.98-0.85 (m, 12H), δ 0.27 (d, 6H); LC ESI MS[M+H + ]:854.778 m / z Example 153 Synthesis of (Z)-17-heptyl-7-(4-hydroxybutyl)-15,15-dimethyl-14,16,18-trioxa-7-aza-15-silaheptacos-21-en-1-yl 2-hexyldecanoate [ka]

[0240] (Z)-17-heptyl-7-(4-hydroxybutyl)-15,15-dimethyl-14,16,18-trioxa-7-aza-15-silaheptacos-21-en-1-yl 2-hexyldecanoate was prepared from (Z)-1-bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silaicos-14-ene (1.073 g, 2.057 mmol, 1.1 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (800 mg, 1.870 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (350 mg, 0.410 mmol, 22% yield). 1H NMR (500 MHz, benzene-d6) δ 5.63-5.49 (m, 2H), δ 5.00 (dt, 1H), δ 4.12 (t, 2H), δ 3.91-3.84 (m, 1H), δ 3.76 (t, 2H), δ 3.62 (t, 2H), δ 3.49-3.39 (m, 1H), δ 2.50-2.41 (m, 3H), δ 2.35-2.23 (m, 5H), δ2.10-2.03 (m, 2H), δ 1.93-1.75 (m, 4H) δ 1.68-1.12 (br. m, 60H), δ0.95-0.85 (m, 12H), δ 0.27 (d, 6H); LC ESI MS [M+H + ]:854.778 m / z Example 154 Synthesis of 7-(4-hydroxybutyl)-15,15,17-trimethyl-14,16,18-trioxa-7-aza-15-silaoctacosyl 2-hexyldecanoate [ka]

[0241] 7-(4-Hydroxybutyl)-15,15,17-trimethyl-14,16,18-trioxa-7-aza-15-silaoctacosyl 2-hexyldecanoate was prepared from 1-bromo-8,8,10-trimethyl-7,9,11-trioxa-8-silahenicosane (700.88 mg, 1.595 mmol, 1.1 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (620 mg, 1.445 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (146 mg, 0.186 mmol, 13% yield). 1H NMR (500 MHz, benzene-d6) δ 5.09 (q, 1H), δ 4.12 (t, 2H), δ 3.85-3.79 (m, 1H), δ 3.73 (t, 2H), δ 3.62 (t, 2H), δ3.40-3.35 (m, 1H), δ 2.51-2.45 (m, 1H), δ 2.34-2.23 (m, 6H), δ1.85-1.76 (m, 2H), δ 1.70-1.14 (br. m, 62H), δ 0.93-0.87 (m, 9H), δ 0.24 (d, 6H); LC ESI MS [M+H + ]:786.693 m / z Example 155 Synthesis of 7-(4-hydroxybutyl)-15,15-dimethyl-17-propyl-14,16,18-trioxa-7-aza-15-silaoctacosyl 2-hexyldecanoate [ka]

[0242] 7-(4-Hydroxybutyl)-15,15-dimethyl-17-propyl-14,16,18-trioxa-7-aza-15-silaoctacosyl 2-hexyldecanoate was prepared from 1-bromo-8,8-dimethyl-10-propyl-7,9,11-trioxa-8-silahenicosane (721.56 mg, 1.543 mmol, 1.1 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (600 mg, 1.403 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (248 mg, 0.305 mmol, 22% yield). 1H NMR (500 MHz, benzene-d6) δ 4.97 (t, 1H), δ 4.11 (t, 2H), δ 3.87-3.81 (m, 1H), δ 3.75 (t, 2H), δ 3.61 (t, 2H), δ3.42-3.37 (m, 1H), TOF MS ES + [M+H + ]:814.7308 m / z Example 156 Synthesis of 7-(4-hydroxybutyl)-15,15-dimethyl-17-propyl-14,16,18-trioxa-7-aza-15-silatriacontyl 2-hexyldecanoate [ka]

[0243] 7-(4-Hydroxybutyl)-15,15-dimethyl-17-propyl-14,16,18-trioxa-7-aza-15-silatriacontyl 2-hexyldecanoate was prepared from 1-bromo-8,8-dimethyl-10-propyl-7,9,11-trioxa-8-silatricosane (903.91 mg, 1.824 mmol, 1.2 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (650 mg, 1.520 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (285 mg, 0.338 mmol, 22% yield). H NMR (500 MHz, benzene-d6) δ 4.97 (t, 1H), δ 4.11 (t, 2H), δ 3.89-3.81 (m, 1H), δ 3.75 (t, 2H), δ 3.62 (t, 2H), δ 3.44-3.37 (m, 1H), δ 2.50-2.42 (m, 1H), δ 2.36-2.23 (m, 6H), δ1.89-1.15 (br. m, 68H), δ 0.96-0.90 (m, 12H) δ 0.26 (d, 6H); LC ESI MS[M+H + ]:842.890 m / z Example 157 Synthesis of 14-(4-hydroxybutyl)-6,6-dimethyl-4-nonyl-3,5,7-trioxa-14-aza-6-silaycosan-20-yl 2-hexyldecanoate [ka]

[0244] 14-(4-Hydroxybutyl)-6,6-dimethyl-4-nonyl-3,5,7-trioxa-14-aza-6-silaicosan-20-yl 2-hexyldecanoate was prepared from 13-bromo-6,6-dimethyl-4-nonyl-3,5,7-trioxa-6-silatridecane (644.36 mg, 1.466 mmol, 1.1 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (570 mg, 1.33 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (100 mg, 0.127 mmol, 10% yield). 1H NMR (500 MHz, benzene-d6) δ 4.97 (dt, 1H), δ 4.12 (t, 2H), δ 3.87-3.80 (m, 1H), δ 3.75 (t, 2H), δ 3.62 (t, 2H), δ3.45-3.35 (m, 1H), δ 2.50-2.43 (m, 1H), δ 2.35-2.23 (m, 6H), δ1.94-1.72 (m, 4H), δ 1.65-1.14 (br. m, 60H), δ 0.95-0.88 (m, 9H), δ 0.26 (d, 6H); TOF MS ES + [M+H + ]:786.7024 m / z Example 158 Synthesis of 14-(4-hydroxybutyl)-6,6-dimethyl-4-undecyl-3,5,7-trioxa-14-aza-6-silaycosan-20-yl 2-hexyldecanoate [ka]

[0245] 14-(4-Hydroxybutyl)-6,6-dimethyl-4-undecyl-3,5,7-trioxa-14-aza-6-silaicosan-20-yl 2-hexyldecanoate was prepared from 13-bromo-6,6-dimethyl-4-undecyl-3,5,7-trioxa-6-silatridecane (829.38 mg, 1.543 mmol, 1.1 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (600 mg, 1.403 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (190 mg, 0.233 mmol, 17% yield). 1H NMR (500 MHz, benzene-d6) δ 4.97 (t, 1H), δ 4.11 (t, 2H), δ 3.83-3.80 (m, 1H), δ 3.74 (t, 2H), δ 3.62 (t, 2H), δ3.43-3.34 (m, 1H), δ 2.49-2.42 (m, 1H), δ 2.33-2.25 (m, 6H), δ1.92-1.76 (m, 4H), δ 1.65-1.14 (br. m, 63H), δ 0.98-0.85 (m, 9H), δ 0.25 (d, 6H); LC ESI MS [M+H + ]:814.747 m / z Example 159 Synthesis of 17-heptyl-15,15-dimethyl-7-(2-(1-methylpyrrolidin-2-yl)ethyl)-14,16,18-trioxa-7-aza-15-silahexacosyl 2-hexyldecanoate [ka]

[0246] 17-Heptyl-15,15-dimethyl-7-(2-(1-methylpyrrolidin-2-yl)ethyl)-14,16,18-trioxa-7-aza-15-silahexacosyl 2-hexyldecanoate was prepared from 1-bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silanonadecane (233.6 mg, 0.471 mmol, 1.0 equiv.) and 6-((2-(1-methylpyrrolidin-2-yl)ethyl)amino)hexyl 2-hexyldecanoate (220 mg, 0.471 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (72 mg, 0.082 mmol, 17% yield). 1H NMR (500 MHz, benzene-d6) δ 5.01 (dt, 1H), δ 4.13 (t, 2H), δ 3.91-3.84 (m, 1H), δ 3.78 (t, 2H), δ 3.45-3.40 (m, 1H), δ 3.00 (t, 1H) TOF MS ES + [M+H + ]:881.8089 m / z Example 160 Synthesis of 16-heptyl-14,14-dimethyl-7-(2-(1-methylpyrrolidin-2-yl)ethyl)-15,17-dioxa-7-aza-14-silapentacosyl 2-hexyldecanoate [ka]

[0247] 16-Heptyl-14,14-dimethyl-7-(2-(1-methylpyrrolidin-2-yl)ethyl)-15,17-dioxa-7-aza-14-silapentacosyl 2-hexyldecanoate was prepared from (6-bromohexyl)dimethyl((1-(octyloxy)octyl)oxy)silane (81.76 mg, 0.170 mmol, 1.14 equiv.) and 6-((2-(1-methylpyrrolidin-2-yl)ethyl)amino)hexyl 2-hexyldecanoate (70.00 mg, 0.15 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (40 mg, 0.046 mmol, 31% yield). 1H NMR (500 MHz, benzene-d6) δ 4.89 (t, 1H), δ 4.13 (t, 2H), δ 3.78-3.74 (m, 1H), δ 3.41-3.36 (m, 1H), δ 3.00 (td, 1H) δ2.54-2.38 (m, 6H), δ 2.29 (s, 3H), δ 2.12-1.93 (m, 3H) δ1.89-1.20 (br. m, 70H), δ 0.94-0.88 (m, 12H), δ 0.78-0.73 (m, 2H) δ 0.29 (d, 6H) Example 161 Synthesis of 16-(4-hydroxybutyl)-8,8-dimethyl-6-nonyl-5,7,9-trioxa-16-aza-8-siladocosan-22-yl 2-hexyldecanoate [ka]

[0248] 16-(4-Hydroxybutyl)-8,8-dimethyl-6-nonyl-5,7,9-trioxa-16-aza-8-siladocosan-22-yl 2-hexyldecanoate was prepared from 15-bromo-8,8-dimethyl-6-nonyl-5,7,9-trioxa-8-silapentadecane (661.41 mg, 1.414 mmol, 1.1 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (550 mg, 1.286 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (112 mg, 0.137 mmol, 11% yield). 1H NMR (500 MHz, benzene-d6) δ 4.99 (dt, 1H), δ 4.12 (t, 2H), δ 3.88-3.80 (m, 1H), δ 3.77 (t, 2H), δ 3.62 (t, 2H), δ3.43-3.36 (m, 1H), δ 2.51-2.44 (m, 1H), δ 2.35-2.23 (m, 6H), δ1.97-1.76 (m, 4H), δ 1.68-1.13 (br. m, 60H), δ 0.94-0.89 (m, 12H), δ 0.29 (d, 6H); LC ESI MS [M+H + ]:814.702 m / z Example 162 Synthesis of 16-(4-hydroxybutyl)-8,8-dimethyl-6-undecyl-5,7,9-trioxa-16-aza-8-siladocosan-22-yl 2-hexyldecanoate [ka]

[0249] 16-(4-Hydroxybutyl)-8,8-dimethyl-6-undecyl-5,7,9-trioxa-16-aza-8-siladocosan-22-yl 2-hexyldecanoate was prepared from 15-bromo-8,8-dimethyl-6-undecyl-5,7,9-trioxa-8-silapentadecane (411.21 mg, 0.772 mmol, 1.1 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (300 mg, 0.702 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (186 mg, 0.221 mmol, 32% yield). 1H NMR (500 MHz, benzene-d6) δ 4.99 (dt, 1H), δ 4.12 (t, 2H), δ 3.94-3.80 (m, 1H), δ 3.76 (t, 2H), δ 3.62 (t, 2H), δ3.43-3.36 (m, 1H), δ 2.52-2.38 (m, 1H), δ 2.36-2.24 (m, 6H), δ1.97-1.75 (m, 4H), δ 1.68-1.10 (br. m, 64H), δ 0.95-0.85 (m, 12H), δ 0.27 (d, 6H); TOF MS ES + [M+H + ]:842.7631 m / z Example 163 Synthesis of 14-(4-hydroxybutyl)-4,6,6-trimethyl-3,5,7-trioxa-14-aza-6-silaycosan-20-yl 2-hexyldecanoate [ka]

[0250] 14-(4-Hydroxybutyl)-4,6,6-trimethyl-3,5,7-trioxa-14-aza-6-silaicosan-20-yl 2-hexyldecanoate was prepared from 13-bromo-4,6,6-trimethyl-3,5,7-trioxa-6-silatridecane (311.48 mg, 0.952 mmol, 1.1 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-hexyldecanoate (370 mg, 0.865 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (170 mg, 0.252 mmol, 29% yield). 1H NMR (500 MHz, benzene-d6) δ 5.04 (q, 1H), δ 4.11 (t, 2H), δ 3.82-3.72 (m, 1H), δ 3.70 (t, 2H), δ 3.62 (t, 2H), δ3.37-3.27 (m, 1H), δ 2.52-2.38 (m, 1H), δ 2.34-2.23 (m, 6H), δ1.86-1.75 (m, 2H), δ 1.66-1.10 (br. m, 48H), δ 0.94-0.87 (m, 6H), δ 0.21 (s, 6H); TOF MS ES + [M+H + ]:674.5767 m / z Example 164 Synthesis of 17-heptyl-7-(3-hydroxypropyl)-15,15-dimethyl-14,16,18-trioxa-7-aza-15-silahexacosyl 2-hexyldecanoate [ka]

[0251] 17-Heptyl-7-(3-hydroxypropyl)-15,15-dimethyl-14,16,18-trioxa-7-aza-15-silahexacosyl 2-hexyldecanoate was prepared from 1-bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silanonadecane (498.19 mg, 1.00 mmol, 1.1 equiv.) and 6-((3-hydroxypropyl)amino)hexyl 2-hexyldecanoate (378.02 mg, 0.914 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (50 mg, 0.060 mmol, 6% yield). 1H NMR (500 MHz, benzene-d6) δ 5.01 (dt, 1H), δ 4.12 (t, 2H), δ 3.91-3.82 (m, 1H), δ 3.75 (t, 2H), δ 3.46-3.38 (m, 1H), δ2.52-2.43 (m, TOF MS ES + [M+H + ]:828.7505 m / z Example 165 Synthesis of 16-heptyl-7-(2-hydroxyethyl)-14,14-dimethyl-15,17-dioxa-7-aza-14-silapentacosyl 2-hexyldecanoate [ka]

[0252] 16-Heptyl-7-(2-hydroxyethyl)-14,14-dimethyl-15,17-dioxa-7-aza-14-silapentacosyl 2-hexyldecanoate was prepared from (6-bromohexyl)dimethyl((1-(octyloxy)octyl)oxy)silane (263.80 mg, 0.550 mmol, 1.1 equiv.) and 6-((2-hydroxyethyl)amino)hexyl 2-hexyldecanoate (200 mg, 0.500 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (180 mg, 0.225 mmol, 45% yield). 1H NMR (500 MHz, benzene-d6) δ 4.90-4.87 (m, 1H), δ 4.12 (t, 2H), δ 3.79-3.74 (m, 1H), δ 3.51 (t, 2H), δ 3.46-3.36 (m, 2H), δ2.51-2.46 (m, 1H), δ 2.39-2.26 (m, 6H), δ 1.88-1.73 (m, 4H), δ1.69-1.18 (br. m, 62H), δ 0.94-0.87 (m, 12H), δ 0.26 (d, 6H); TOF MS ES + [M+H + ]:798.7377 m / z Example 166 Synthesis of 6-((6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)(4-hydroxybutyl)amino)hexyl 2-(decylthio)hexanoate [ka]

[0253] 6-((6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)(4-hydroxybutyl)amino)hexyl 2-(decylthio)hexanoate was prepared from 4-((6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)amino)butan-1-ol (150.00 mg, 0.307 mmol, 1.0 equiv.) and 6-oxohexyl 2-(decylthio)hexanoate (118.87 mg, 0.307 mmol, 1.0 equiv.) according to general procedure J. The crude product was purified twice by flash column chromatography according to purification methods A and B to give the pure product as a colorless oil (130 mg, 0.151 mmol, 49% yield). 1H NMR (500 MHz, benzene-d6) δ 4.89 (dt, 1H), δ4.17-4.06 (m, 2H), δ 3.79-3.73 (m, 1H), δ 3.62 (t, 2H), δ 3.42-3.30 (m, 2H), δ2.78-2.71 (m, 1H), δ 2.67-2.60 (m, 1H), δ 2.35-2.23 (m, 6H), δ2.09-1.99 (m, 1H), δ 1.89-1.11 (m, 65H), δ 0.94-0.89 (m, 9H), δ 0.83 (t, 3H), δ 0.77-0.72 (m, 2H), δ 0.26 (d, 6H); TOF MS ES + [M+H + ]:858.7409 m / z Example 167 Synthesis of 15-heptyl-7-(4-hydroxybutyl)-17,17-dimethyl-14,16-dioxa-7-aza-17-silapentacosyl 2-(decylthio)hexanoate [ka]

[0254] 15-Heptyl-7-(4-hydroxybutyl)-17,17-dimethyl-14,16-dioxa-7-aza-17-silapentacosyl 2-(decylthio)hexanoate was prepared from 13-heptyl-15,15-dimethyl-12,14-dioxa-5-aza-15-silatricosan-1-ol (150.00 mg, 0.307 mmol, 1.0 equiv.) and 6-oxohexyl 2-(decylthio)hexanoate (118.87 mg, 0.307 mmol, 1.0 equiv.) according to general procedure J. The crude product was purified twice by flash column chromatography according to purification methods A and B to give the pure product as a colorless oil (142 mg, 0.165 mmol, 54% yield). 1H NMR (500 MHz, benzene-d6) δ 4.88 (dt, 1H), δ4.16-4.07 (m, 2H), δ 3.79-3.73 (m, 1H), δ 3.62 (t, 2H), δ3.41-3.30 (m, 2H), δ 2.77-2.70 (m, 1H), δ 2.67-2.60 (m, 1H), δ2.34-2.23 (m, 6H), δ 2.08-1.99 (m, 1H), δ 1.88-1.12 (m, 65H), δ0.94-0.88 (m, 9H), δ 0.83 (t, 3H), δ 0.76-0.72 (m, 2H), δ 0.25 (d, 6H); TOF MS ES + [M+H + ]:858.7404 m / z Example 168 Synthesis of 7-(4-hydroxybutyl)-15,15-dimethyl-13-(octyloxy)-14,16-dioxa-7-aza-15-silatetracosyl 2-(decylthio)hexanoate [ka]

[0255] 7-(4-Hydroxybutyl)-15,15-dimethyl-13-(octyloxy)-14,16-dioxa-7-aza-15-silatetracosyl 2-(decylthio)hexanoate was prepared from 12-(5-bromopentyl)-10,10-dimethyl-9,11,13-trioxa-10-silahenicosane (177.88 mg, 0.359 mmol, 1.1 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-(decylthio)hexanoate (150.00 mg, 0.326 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified twice by flash column chromatography according to purification method A to give the pure product as a colorless oil (140 mg, 0.160 mmol, 49% yield). 1H NMR (500 MHz, benzene-d6) δ 5.01 (dt, 1H), δ4.16-4.06 (m, 2H), δ 3.89-3.84 (m, 1H), δ 3.77 (t, 2H), δ 3.62 (t, 2H), δ 3.45-3.30 (m, 2H), δ 2.77-2.70 (m, 1H), δ 2.67-2.60 (m, 1H), δ2.37-2.19 (m, 6H), δ 2.08-1.99 (m, 1H), δ 1.95-1.09 (m, 65H), δ0.95-0.87 (m, 9H), δ 0.83 (t, 3H), δ 0.28 (d, 6H); TOF MS ES + [M+H + ]:874.7339 m / z Example 169 Synthesis of 15-heptyl-7-(4-hydroxybutyl)-17,17-dimethyl-14,16,18-trioxa-7-aza-17-silahexacosyl 2-(decylthio)hexanoate [ka]

[0256] 15-Heptyl-7-(4-hydroxybutyl)-17,17-dimethyl-14,16,18-trioxa-7-aza-17-silahexacosyl 2-(decylthio)hexanoate was prepared from 1-bromo-8-heptyl-10,10-dimethyl-7,9,11-trioxa-10-silanonadecane (161.71 mg, 0.326 mmol, 1.0 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-(decylthio)hexanoate (150.00 mg, 0.326 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified twice by flash column chromatography according to purification method A to give the pure product as a colorless oil (123 mg, 0.141 mmol, 43% yield). 1H NMR (500 MHz, benzene-d6) δ 5.01 (dt, 1H), δ4.16-4.07 (m, 2H), δ 3.93-3.84 (m, 1H), δ 3.77 (t, 2H), δ 3.62 (t, 2H), δ 3.45-3.30 (m, 2H), δ 3.78-3.71 (m, 1H), δ 2.67-2.60 (m, 1H), δ 2.34-2.23 (m, 6H), δ 2.09-2.00 (m, 1H), δ 1.95-1.11 (m, 65H), δ 0.94-0.89 (m, 9H), δ 0.83 (t, 3H), δ 0.28 (d, 6H); TOF MS ES + [M+H + ]:874.7355 m / z Example 170 Synthesis of 6-((4-hydroxybutyl)(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)hexyl)amino)hexyl 2-(decylthio)hexanoate [ka]

[0257] 6-((4-Hydroxybutyl)(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)hexyl)amino)hexyl 2-(decylthio)hexanoate was prepared according to general procedure K from 1-((6-bromo-1-(octyloxy)hexyl)oxy)-1,1,3,3-tetramethyl-3-octyldisiloxane (156.59 mg, 0.2828 mmol, 1.0 equiv) and 6-((4-hydroxybutyl)amino)hexyl 2-(decylthio)hexanoate (130.00 mg, 0.2828 mmol, 1.0 equiv). The crude product was purified twice by flash column chromatography according to purification method B to give the pure product as a colorless oil (152 mg, 0.163 mmol, 58% yield). 1H NMR (500 MHz, benzene-d6) δ 5.00 (dt, 1H), δ4.17-4.05 (m, 2H), δ 3.90-3.82 (m, 1H), δ 3.61 (t, 2H), δ3.46-3.28 (m, 2H), δ 3.78-3.58 (m, 2H), δ 2.36-2.23 (m, 6H), δ2.09-1.97 (m, 1H), δ 1.93-1.09 (m, 65H), δ 0.94-0.88 (m, 9H), δ 0.83 (t, 3H), δ 0.70-0.65 (m, 2H), δ 0.27 (d, 6H), δ 0.21 (d, 6H); TOF MS ES + [M+H + ]:932.7584 m / z Example 171 Synthesis of 15-heptyl-7-(4-hydroxybutyl)-17,17,19,19-tetramethyl-14,16,18-trioxa-7-aza-17,19-disilaheptacosyl 2-(decylthio)hexanoate [ka]

[0258] 15-Heptyl-7-(4-hydroxybutyl)-17,17,19,19-tetramethyl-14,16,18-trioxa-7-aza-17,19-disilaheptacosyl 2-(decylthio)hexanoate was prepared from 1-((1-((6-bromohexyl)oxy)octyl)oxy)-1,1,3,3-tetramethyl-3-octyldisiloxane (177.88 mg, 0.321 mmol, 0.98 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-(decylthio)hexanoate (150.00 mg, 0.326 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified twice by flash column chromatography according to purification method A to give the pure product as a colorless oil (184 mg, 0.197 mmol, 60% yield). 1H NMR (500 MHz, benzene-d6) δ 5.00 (t, 1H), δ4.16-4.05 (m, 2H), δ 3.89-3.84 (m, 1H), δ 3.62 (t, 2H), δ3.45-3.39 (m, 1H), δ 3.34-3.30 (m, 1H), δ 3.77-3.70 (m, 1H), δ2.67-2.60 (m, 1H), δ 2.34-2.23 (m, 6H), δ 2.08-1.99 (m, 1H), δ1.95-1.12 (m, 65H), δ 0.95-0.89 (m, 9H), δ 0.83 (t, 3H), δ0.71-0.65 (m, 2H), δ 0.27 (d, 6H), δ 0.21 (d, 6H); TOF MS ES + [M+H + ]:932.7599 m / z Example 172 Synthesis of 6-((4-hydroxybutyl)(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)hexyl)amino)hexyl 2-(decylthio)hexanoate [ka]

[0259] 6-((4-Hydroxybutyl)(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)hexyl)amino)hexyl 2-(decylthio)hexanoate was prepared from 4-((6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)hexyl)amino)butan-1-ol (90.00 mg, 0.159 mmol, 1.0 equiv) and 6-oxohexyl 2-(decylthio)hexanoate (61.54 mg, 0.159 mmol, 1.0 equiv) according to general procedure J. The crude product was purified twice by flash column chromatography according to purification methods A and B to give the pure product as a colorless oil (40 mg, 0.042 mmol, 26% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.04 (dt, 1H), δ4.16-4.06 (m, 2H), δ 3.91-3.86 (m, 1H), δ 3.76 (t, 2H), δ 3.62 (t, 2H), δ 3.47-3.40 (m, 1H), δ 3.34-3.30 (m, 1H), δ 2.77-2.71 (m, 1H), δ2.67-2.60 (m, 1H), δ 2.37-2.21 (m, 6H), δ 2.11-1.98 (m, 1H), δ1.95-1.11 (m, 65H), δ 0.94-0.89 (m, 9H), δ 0.83 (t, 3H), δ 0.31 (d, 6H), δ 0.25 (s, 6H); TOF MS ES + [M+H + ]:948.7556 m / z Example 173 Synthesis of 15-heptyl-7-(4-hydroxybutyl)-17,17,19,19-tetramethyl-14,16,18,20-tetraoxa-7-aza-17,19-disilaoctacosyl 2-(decylthio)hexanoate [ka]

[0260] 15-Heptyl-7-(4-hydroxybutyl)-17,17,19,19-tetramethyl-14,16,18,20-tetraoxa-7-aza-17,19-disilaoctacosyl 2-(decylthio)hexanoate was prepared from 1-((1-((6-bromohexyl)oxy)octyl)oxy)-1,1,3,3-tetramethyl-3-(octyloxy)disiloxane (204.49 mg, 0.359 mmol, 1.1 equiv) and 6-((4-hydroxybutyl)amino)hexyl 2-(decylthio)hexanoate (150.00 mg, 0.326 mmol, 1.0 equiv) according to general procedure K. The crude product was purified twice by flash column chromatography according to purification method A to give the pure product as a colorless oil (192 mg, 0.202 mmol, 62% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.04 (dt, 1H), δ4.16-4.06 (m, 2H), δ 3.90-3.85 (m, 1H), δ 3.76 (t, 2H), δ 3.62 (t, 2H), δ 3.46-3.40 (m, 1H), δ 3.33-3.30 (m, 1H), δ 2.77-2.70 (m, 1H), δ2.67-2.60 (m, 1H), δ 2.34-2.23 (m, 6H), δ 2.08-1.99 (m, 1H), δ1.96-1.12 (m, 65H), δ 0.95-0.88 (m, 9H), δ 0.83 (t, 3H), δ 0.31 (d, 6H), δ 0.24 (s, 6H); ; TOF MS ES + [M+H + ]:948.7554 m / z Example 174 Synthesis of 18-hexyl-7-(4-hydroxybutyl)-15,15-dimethyl-13-(octyloxy)-14,16-dioxa-7-aza-15-silahexacosyl 2-(decylthio)hexanoate [ka]

[0261] 18-Hexyl-7-(4-hydroxybutyl)-15,15-dimethyl-13-(octyloxy)-14,16-dioxa-7-aza-15-silahexacosyl 2-(decylthio)hexanoate was prepared from 10-(5-bromopentyl)-15-hexyl-12,12-dimethyl-9,11,13-trioxa-12-silatricosane (218.15 mg, 0.359 mmol, 1.1 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-(decylthio)hexanoate (150.00 mg, 0.326 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified twice by flash column chromatography according to purification method A to give the pure product as a colorless oil (158 mg, 0.160 mmol, 49% yield). 1H NMR (500 MHz, benzene-d6) δ 5.03 (dt, 1H), δ4.16-4.07 (m, 2H), δ 3.92-3.86 (m, 1H), δ 3.76 (d, 2H), δ 3.62 (t, 2H), δ 3.48-3.42 (m, 1H), δ 3.34-3.30 (m, 1H), δ 2.77-2.70 (m, 1H), δ2.67-2.60 (m, 1H), δ 2.36-2.24 (m, 6H), δ 2.08-1.99 (m, 1H), δ1.97-1.12 (m, 78H), δ 0.95-0.89 (m, 12H), δ 0.83 (t, 3H), δ 0.30 (d, 6H); TOF MS ES + [M+H + ]:986.8613 m / z Example 175 Synthesis of 15-heptyl-20-hexyl-7-(4-hydroxybutyl)-17,17-dimethyl-14,16,18-trioxa-7-aza-17-silaoctacosyl 2-(decylthio)hexanoate [ka]

[0262] 15-Heptyl-20-hexyl-7-(4-hydroxybutyl)-17,17-dimethyl-14,16,18-trioxa-7-aza-17-silaoctacosyl 2-(decylthio)hexanoate was prepared from 1-bromo-8-heptyl-13-hexyl-10,10-dimethyl-7,9,11-trioxa-10-silahenicosane (218.15 mg, 0.359 mmol, 1.1 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-(decylthio)hexanoate (150.00 mg, 0.326 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified twice by flash column chromatography according to purification method A to give the pure product as a colorless oil (190 mg, 0.193 mmol, 59% yield). 1H NMR (500 MHz, benzene-d6) δ 5.02 (dt, 1H), δ4.16-4.07 (m, 2H), δ 3.92-3.85 (m, 1H), δ 3.75 (d, 2H), δ 3.62 (t, 2H), δ 3.46-3.40 (m, 1H), δ 3.34-3.30 (m, 1H), δ 2.77-2.70 (m, 1H), δ2.67-2.60 (m, 1H), δ 2.34-2.24 (m, 6H), δ 2.08-1.99 (m, 1H), δ1.96-1.12 (m, 78H), δ 0.96-0.89 (m, 12H), δ 0.83 (t, 3H), δ 0.30 (d, 6H); LC ESI MS [M+H + ]:986.763 m / z Example 176 Synthesis of 17-heptyl-7-(4-hydroxybutyl)-15,15-dimethyl-14,16,18-trioxa-7-aza-15-silahexacosyl 2-(decylthio)hexanoate [ka]

[0263] 17-Heptyl-7-(4-hydroxybutyl)-15,15-dimethyl-14,16,18-trioxa-7-aza-15-silahexacosyl 2-(decylthio)hexanoate was prepared from 1-bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silanonadecane (177.88 mg, 0.359 mmol, 1.1 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-(decylthio)hexanoate (150.00 mg, 0.326 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified twice by flash column chromatography according to purification method A to give the pure product as a colorless oil (94 mg, 0.107 mmol, 33% yield). 1H NMR (500 MHz, benzene-d6) δ 5.00 (dt, 1H), δ 4.16-4.07 (m, 2H), δ3.89-3.84 (m, 1H), δ 3.77 (t, 2H), δ 3.62 (t, 2H), δ3.45-3.37 (m, 1H), δ 3.34-3.30 (m, 1H), δ 2.77-2.70 (m, 1H), δ2.67-2.60 (m, 1H), δ 2.34-2.24 (m, 6H), δ 2.08-1.99 (m, 1H), δ1.95-1.12 (m, 65H), δ 0.95-0.87 (m, 9H), δ 0.83 (t, 3H), δ 0.28 (d, 6H); TOF MS ES + [M+H + ]:874.7365 m / z Example 177 Synthesis of 6-((6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)(4-hydroxybutyl)amino)hexyl 2-(pentylthio)decanoate [ka]

[0264] 6-((6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)(4-hydroxybutyl)amino)hexyl 2-(pentylthio)decanoate was prepared from 4-((6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)amino)butan-1-ol (150.00 mg, 0.307 mmol, 1.0 equiv.) and 6-oxohexyl 2-(pentylthio)decanoate (114.56 mg, 0.307 mmol, 1.0 equiv.) according to general procedure J. The crude product was purified twice by flash column chromatography according to purification methods A and B to give the pure product as a colorless oil (120 mg, 0.142 mmol, 46% yield). 1H NMR (500 MHz, benzene-d6) δ 4.89 (t, 1H), δ4.17-4.07 (m, 2H), δ 3.82-3.74 (m, 1H), δ 3.62 (t, 2H), δ3.42-3.33 (m, 2H), δ 2.75-2.69 (m, 1H), δ 2.65-2.58 (m, 1H), δ2.35-2.23 (m, 6H), δ 2.12-2.03 (m, 1H), δ 1.89-1.11 (m, 63H), δ0.95-0.89 (m, 9H), δ 0.84 (t, 3H), δ 0.77-0.73 (m, 2H), δ 0.26 (d, 6H); TOF MS ES + [M+H + ]:844.7249 m / z Example 178 Synthesis of 15-heptyl-7-(4-hydroxybutyl)-17,17-dimethyl-14,16-dioxa-7-aza-17-silapentacosyl 2-(pentylthio)decanoate [ka]

[0265] 15-Heptyl-7-(4-hydroxybutyl)-17,17-dimethyl-14,16-dioxa-7-aza-17-silapentacosyl 2-(pentylthio)decanoate was prepared from 13-heptyl-15,15-dimethyl-12,14-dioxa-5-aza-15-silatricosan-1-ol (150.00 mg, 0.307 mmol, 1.0 equiv.) and 6-oxohexyl 2-(pentylthio)decanoate (114.56 mg, 0.307 mmol, 1.0 equiv.) according to general procedure J. The crude product was purified twice by flash column chromatography according to purification methods A and B to give the pure product as a colorless oil (142 mg, 0.168 mmol, 55% yield). 1H NMR (500 MHz, benzene-d6) δ 4.88 (t, 1H), δ4.17-4.07 (m, 2H), δ 3.79-3.73 (m, 1H), δ 3.62 (t, 2H), δ3.40-3.31 (m, 2H), δ 2.75-2.68 (m, 1H), δ 2.64-2.57 (m, 1H), δ2.37-2.23 (m, 6H), δ 2.11-2.00 (m, 1H), δ 1.86-1.11 (m, 63H), δ0.94-0.91 (m, 9H), δ 0.84 (t, 3H), δ 0.75-0.71 (m, 2H), δ 0.25 (d, 6H); TOF MS ES + [M+H + ]:844.7228 m / z Example 179 Synthesis of 7-(4-hydroxybutyl)-15,15-dimethyl-13-(octyloxy)-14,16-dioxa-7-aza-15-silatetracosyl 2-(pentylthio)decanoate [ka]

[0266] 7-(4-Hydroxybutyl)-15,15-dimethyl-13-(octyloxy)-14,16-dioxa-7-aza-15-silatetracosyl 2-(pentylthio)decanoate was prepared from 12-(5-bromopentyl)-10,10-dimethyl-9,11,13-trioxa-10-silahenicosane (183.47 mg, 0.370 mmol, 1.1 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-(pentylthio)decanoate (150 mg, 0.337 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (132 mg, 0.153 mmol, 46% yield). 1H NMR (500 MHz, benzene-d6) δ 5.01 (t, 1H), δ4.17-4.07 (m, 2H), δ 3.89-3.82 (m, 1H), δ 3.77 (t, 2H), δ 3.62 (t, 2H), δ 3.46-3.28 (m, 2H), δ 2.75-2.68 (m, 1H), δ 2.64-2.58 (m, 1H), δ2.35-2.22 (m, 6H), δ 2.11-2.02 (m, 1H), δ 1.95-1.76 (m, 3H), δ1.71-1.12 (m, 60H), δ 0.94-0.87 (m, 9H), δ 0.84 (t, 3H), δ 0.28 (d, 6H); TOF MS ES + [M+H + ]:860.7214 m / z Example 180 Synthesis of 15-heptyl-7-(4-hydroxybutyl)-17,17-dimethyl-14,16,18-trioxa-7-aza-17-silahexacosyl 2-(pentylthio)decanoate [ka]

[0267] 15-Heptyl-7-(4-hydroxybutyl)-17,17-dimethyl-14,16,18-trioxa-7-aza-17-silahexacosyl 2-(pentylthio)decanoate was prepared from 1-bromo-8-heptyl-10,10-dimethyl-7,9,11-trioxa-10-silanonadecane (166.79 mg, 0.336 mmol, 1.0 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-(pentylthio)decanoate (150 mg, 0.336 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (100 mg, 0.116 mmol, 35% yield). 1H NMR (500 MHz, benzene-d6) δ 5.00 (t, 1H), δ4.17-4.07 (m, 2H), δ 3.89-3.83 (m, 1H), δ 3.76 (t, 2H), δ 3.62 (t, 2H), δ 3.44-3.32 (m, 2H), δ 2.75-2.68 (m, 1H), δ 2.64-2.57 (m, 1H), δ2.33-2.23 (m, 6H), δ 2.11-2.01 (m, 1H), δ 1.95-1.76 (m, 3H), δ1.71-1.13 (m, 60H), δ 0.94-0.87 (m, 9H), δ 0.84 (t, 3H), δ 0.28 (d, 6H); TOF MS ES + [M+H + ]:860.7202 m / z Example 181 Synthesis of 6-((4-hydroxybutyl)(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)hexyl)amino)hexyl 2-(pentylthio)decanoate [ka]

[0268] 6-((4-Hydroxybutyl)(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)hexyl)amino)hexyl 2-(pentylthio)decanoate was prepared from 1-((6-bromo-1-(octyloxy)hexyl)oxy)-1,1,3,3-tetramethyl-3-octyldisiloxane (186.36 mg, 0.337 mmol, 1.0 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-(pentylthio)decanoate (150 mg, 0.337 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (120 mg, 0.131 mmol, 39% yield). 1H NMR (500 MHz, benzene-d6) δ 5.00 (t, 1H), δ4.18-4.05 (m, 2H), δ 3.90-3.82 (m, 1H), δ 3.61 (t, 2H), δ3.46-3.30 (m, 2H), δ 2.75-2.55 (m, 2H), δ 2.36-2.23 (m, 6H), δ2.12-1.99 (m, 1H), δ 1.94-1.73 (m, 3H) δ 1.70-1.12 (m, 60H), δ0.95-0.88 (m, 9H), δ 0.84 (t, 3H), δ 0.70-0.65 (m, 2H), δ 0.27 (d, 6H), δ 0.21 (s, 6H); TOF MS ES + [M+H + ]:918.7435 m / z Example 182 Synthesis of 15-heptyl-7-(4-hydroxybutyl)-17,17,19,19-tetramethyl-14,16,18-trioxa-7-aza-17,19-disilaheptacosyl 2-(pentylthio)decanoate [ka]

[0269] 15-Heptyl-7-(4-hydroxybutyl)-17,17,19,19-tetramethyl-14,16,18-trioxa-7-aza-17,19-disilaheptacosyl 2-(pentylthio)decanoate was prepared from 1-((1-((6-bromohexyl)oxy)octyl)oxy)-1,1,3,3-tetramethyl-3-octyldisiloxane (161.52 mg, 0.292 mmol, 1.0 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-(pentylthio)decanoate (130 mg, 0.292 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (122 mg, 0.133 mmol, 45% yield). 1H NMR (500 MHz, benzene-d6) δ 5.01 (t, 1H), δ4.18-4.05 (m, 2H), δ 3.89-3.82 (m, 1H), δ 3.62 (t, 2H), δ3.45-3.31 (m, 2H), δ 2.76-2.56 (m, 2H), δ 2.34-2.23 (m, 6H), δ 2.12-2.00 (m, 1H), δ 1.96-1.12 (m, 63H), δ 0.94-0.88 (m, 9H), δ 0.84 (t, 3H), δ0.70-0.65 (m, 2H), δ 0.27 (d, 6H), δ 0.21 (s, 6H); TOF MS ES + [M+H + ]:918.7426 m / z Example 183 Synthesis of 6-((4-hydroxybutyl)(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)hexyl)amino)hexyl 2-(pentylthio)decanoate [ka]

[0270] 6-((4-Hydroxybutyl)(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)hexyl)amino)hexyl 2-(pentylthio)decanoate was prepared from 4-((6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)hexyl)amino)butan-1-ol (121.00 mg, 0.209 mmol, 1.0 equiv) and 6-oxohexyl 2-(pentylthio)decanoate (78.00 mg, 0.209 mmol, 1.0 equiv) according to general procedure J. The crude product was purified twice by flash column chromatography according to purification methods A and B to give the pure product as a colorless oil (53 mg, 0.057 mmol, 27% yield). 1H NMR (500 MHz, benzene-d6) δ 5.04 (t, 1H), δ4.17-4.07 (m, 2H), δ 3.91-3.86 (m, 1H), δ 3.76 (t, 2H), δ 3.62 (t, 2H), δ 3.47-3.33 (m, 2H), δ 2.75-2.68 (m, 1H), δ 2.65-2.58 (m, 1H), δ2.36-2.23 (m, 6H), δ 2.12-2.02 (m, 1H), δ 1.97-1.11 (m, 63H), δ0.93-0.89 (m, 9H), δ 0.84 (t, 3H), δ 0.32 (d, 6H), δ 0.25 (s, 6H); TOF MS ES + [M+H + ]:934.7384 m / z Example 184 Synthesis of 15-heptyl-7-(4-hydroxybutyl)-17,17,19,19-tetramethyl-14,16,18,20-tetraoxa-7-aza-17,19-disilaoctacosyl 2-(pentylthio)decanoate [ka]

[0271] 15-Heptyl-7-(4-hydroxybutyl)-17,17,19,19-tetramethyl-14,16,18,20-tetraoxa-7-aza-17,19-disilaoctacosyl 2-(pentylthio)decanoate was prepared from 1-((1-((6-bromohexyl)oxy)octyl)oxy)-1,1,3,3-tetramethyl-3-(octyloxy)disiloxane (182.80 mg, 0.321 mmol, 1.1 equiv) and 6-((4-hydroxybutyl)amino)hexyl 2-(pentylthio)decanoate (130.00 mg, 0.292 mmol, 1.0 equiv) according to general procedure K. The crude product was purified twice by flash column chromatography according to purification methods A and B to give the pure product as a colorless oil (101 mg, 0.109 mmol, 37% yield). 1H NMR (500 MHz, benzene-d6) δ 5.04 (t, 1H), δ4.17-4.07 (m, 2H), δ 3.90-3.85 (m, 1H), δ 3.76 (t, 2H), δ 3.62 (t, 2H), δ 3.46-3.32 (m, 2H), δ 2.75-2.68 (m, 1H), δ 2.64-2.57 (m, 1H), δ2.34-2.23 (m, 6H), δ 2.11-2.02 (m, 1H), δ 1.96-1.10 (m, 63H), δ0.92-0.89 (m, 9H), δ 0.84 (t, 3H), δ 0.31 (d, 6H), δ 0.24 (s, 6H); TOF MS ES + [M+H + ]:934.7424 m / z Example 185 Synthesis of 18-hexyl-7-(4-hydroxybutyl)-15,15-dimethyl-13-(octyloxy)-14,16-dioxa-7-aza-15-silahexacosyl 2-(pentylthio)decanoate [ka]

[0272] 18-Hexyl-7-(4-hydroxybutyl)-15,15-dimethyl-13-(octyloxy)-14,16-dioxa-7-aza-15-silahexacosyl 2-(pentylthio)decanoate was prepared from 10-(5-bromopentyl)-15-hexyl-12,12-dimethyl-9,11,13-trioxa-12-silatricosane (225.01 mg, 0.370 mmol, 1.1 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-(pentylthio)decanoate (150.00 mg, 0.336 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified twice by flash column chromatography according to purification methods A and B to give the pure product as a colorless oil (130 mg, 0.134 mmol, 40% yield). 1H NMR (500 MHz, benzene-d6) δ 5.03 (t, 1H), δ4.17-4.07 (m, 2H), δ 3.92-3.86 (m, 1H), δ 3.76 (d, 2H), δ 3.62 (t, 2H), δ 3.48-3.32 (m, 2H), δ 2.75-2.68 (m, 1H), δ 2.65-2.58 (m, 1H), δ2.36-2.24 (m, 6H), δ 2.11-2.02 (m, 1H), δ 1.97-1.12 (m, 76H), δ0.96-0.86 (m, 12H), δ 0.84 (t, 3H), δ 0.30 (d, 6H); TOF MS ES + [M+H + ]:972.8441 m / z Example 186 Synthesis of 15-heptyl-20-hexyl-7-(4-hydroxybutyl)-17,17-dimethyl-14,16,18-trioxa-7-aza-17-silaoctacosyl 2-(pentylthio)decanoate [ka]

[0273] 15-Heptyl-20-hexyl-7-(4-hydroxybutyl)-17,17-dimethyl-14,16,18-trioxa-7-aza-17-silaoctacosyl 2-(pentylthio)decanoate was prepared from 1-bromo-8-heptyl-13-hexyl-10,10-dimethyl-7,9,11-trioxa-10-silahenicosane (204.56 mg, 0.336 mmol, 1.0 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-(pentylthio)decanoate (150.00 mg, 0.336 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (161 mg, 0.165 mmol, 49% yield). 1H NMR (500 MHz, benzene-d6) δ 5.03 (t, 1H), δ4.19-4.07 (m, 2H), δ 3.94-3.85 (m, 1H), δ 3.76 (d, 2H), δ 3.62 (t, 2H), δ 3.48-3.32 (m, 2H), δ 2.77-2.57 (m, 2H), δ 2.35-2.23 (m, 6H), δ2.14-2.01 (m, 1H), δ 1.97-1.12 (m, 76H), δ 0.96-0.89 (m, 12H), δ 0.84 (t, 3H), δ 0.30 (s, 6H); TOF MS ES + [M+H + ]:972.8463 m / z Example 187 Synthesis of 16-heptyl-7-(4-hydroxybutyl)-14,14-dimethyl-15,17-dioxa-7-aza-14-silapentacosyl 2-(pentylthio)decanoate [ka]

[0274] 16-Heptyl-7-(4-hydroxybutyl)-14,14-dimethyl-15,17-dioxa-7-aza-14-silapentacosyl 2-(pentylthio)decanoate was prepared from (6-bromohexyl)dimethyl((1-(octyloxy)octyl)oxy)silane (177.55 mg, 0.370 mmol, 1.1 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-(pentylthio)decanoate (150.00 mg, 0.336 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (178 mg, 0.211 mmol, 63% yield). 1H NMR (500 MHz, benzene-d6) δ 4.88 (t, 1H), δ4.17-4.07 (m, 2H), δ 3.79-3.73 (m, 1H), δ 3.63 (t, 2H), δ3.41-3.31 (m, 2H), δ 2.75-2.68 (m, 1H), δ 2.64-2.57 (m, 1H), δ2.37-2.24 (m, 6H), δ 2.11-2.01 (m, 1H), δ 1.88-1.13 (m, 63H), δ0.92-0.89 (m, 9H), δ 0.84 (t, 3H), δ 0.76-0.72 (m, 2H), δ 0.24 (d, 6H); TOF MS ES + [M+H + ]:844.7252 m / z Example 188 Synthesis of 17-heptyl-7-(4-hydroxybutyl)-15,15-dimethyl-14,16,18-trioxa-7-aza-15-silahexacosyl 2-(pentylthio)decanoate [ka]

[0275] 17-Heptyl-7-(4-hydroxybutyl)-15,15-dimethyl-14,16,18-trioxa-7-aza-15-silahexacosyl 2-(pentylthio)decanoate was prepared from 1-bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silanonadecane (183.47 mg, 0.370 mmol, 1.1 equiv.) and 6-((4-hydroxybutyl)amino)hexyl 2-(pentylthio)decanoate (150.00 mg, 0.336 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (79 mg, 0.092 mmol, 27% yield). 1H NMR (500 MHz, benzene-d6) δ 5.00 (t, 1H), δ4.17-4.07 (m, 2H), δ 3.89-3.83 (m, 1H), δ 3.77 (t, 2H), δ 3.62 (t, 2H), δ3.45-3.32 (m, 2H), δ 2.75-2.68 (m, 1H), δ 2.64-2.57 (m, 1H), δ2.34-2.24 (m, 6H), δ 2.11-2.02 (m, 1H), δ 1.95-1.13 (m, 63H), δ0.92-0.89 (m, 9H), δ 0.84 (t, 3H), δ 0.28 (d, 6H); TOF MS ES + [M+H + ]:860.7207 m / z Example 189 Synthesis of heptadecan-9-yl 8-((6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)(2-hydroxyethyl)amino)octanoate [ka]

[0276] Heptadecan-9-yl 8-((6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)(2-hydroxyethyl)amino)octanoate was prepared from ((6-bromo-1(octyloxy)hexyl)oxy)dimethyl(octyl)silane (155.28 mg, 0.324 mmol, 1.1 equiv.) and heptadecan-9-yl 8-((2-hydroxyethyl)amino)octanoate (130.00 mg, 0.294 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified twice by flash column chromatography according to purification method A to give the pure product as a colorless oil (180 mg, 0.214 mmol, 73% yield). 1H NMR (500 MHz, benzene-d6) δ 5.16 (m, 1H), δ 4.88 (t, 1H), δ 3.79-3.72 (m, 1H), δ 3.50 (t, 2H), δ 3.41-3.35 (m, 1H), δ2.37-2.23 (m, TOF MS ES + [M+H + ]:840.7825 m / z Example 190 Synthesis of heptadecan-9-yl 18-(2-hydroxyethyl)-10,10-dimethyl-12-(octyloxy)-9,11-dioxa-18-aza-10-silahexacosane-26-oate [ka]

[0277] Heptadecan-9-yl 18-(2-hydroxyethyl)-10,10-dimethyl-12-(octyloxy)-9,11-dioxa-18-aza-10-silahexacosane-26-oate was prepared from 12-(5-bromopentyl)-10,10-dimethyl-9,11,13-trioxa-10-silahenicosane (160.45 mg, 0.324 mmol, 1.1 equiv.) and heptadecan-9-yl 8-((2-hydroxyethyl)amino)octanoate (130.00 mg, 0.294 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified twice by flash column chromatography according to purification method A to give the pure product as a colorless oil (152 mg, 0.177 mmol, 60% yield). 1H NMR (500 MHz, benzene-d6) δ 5.20-5.14 (m, 1H), δ 5.01 (t, 1H), δ 3.90-3.84 (m, 1H), δ 3.77 (t, 2H), δ 3.50 (t, 2H), δ3.44-3.36 (m, TOF MS ES + [M+H + ]:856.7795 m / z Example 191 Synthesis of heptadecan-9-yl 8-((2-hydroxyethyl)(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)hexyl)amino)octanoate [ka]

[0278] Heptadecan-9-yl 8-((2-hydroxyethyl)(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)hexyl)amino)octanoate was prepared from 1-((6-bromo-1(octyloxy)hexyl)oxy)-1,1,3,3-tetramethyl-3-octyldisiloxane (179.28 mg, 0.324 mmol, 1.1 equiv.) and heptadecan-9-yl 8-((2-hydroxyethyl)amino)octanoate (130.00 mg, 0.294 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified twice by flash column chromatography according to purification method A to give the pure product as a colorless oil (203 mg, 0.222 mmol, 75% yield). 1H NMR (500 MHz, benzene-d6) δ 5.19-5.12 (m, 1H), δ 5.01 (t, 1H), δ 3.89-3.83 (m, 1H), δ 3.50 (t, 2H), δ 3.45-3.38 (m, 1H), TOF MS ES + [M+H + ]:914.7997 m / z Example 192 Synthesis of heptadecan-9-yl 8-((2-hydroxyethyl)(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)hexyl)amino)octanoate [ka]

[0279] Heptadecan-9-yl 8-((2-hydroxyethyl)(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)hexyl)amino)octanoate was prepared from 1-((6-bromo-1(octyloxy)hexyl)oxy)-1,1,3,3-tetramethyl-3-(octyloxy)disiloxane (184.46 mg, 0.324 mmol, 1.1 equiv.) and heptadecan-9-yl 8-((2-hydroxyethyl)amino)octanoate (130.00 mg, 0.294 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified twice by flash column chromatography according to purification method A to give the pure product as a colorless oil (186 mg, 0.200 mmol, 68% yield). 1H NMR (500 MHz, benzene-d6) δ 5.19-5.13 (m, 1H), δ 5.04 (t, 1H), δ 3.91-3.85 (m, 1H), δ 3.75 (t, 2H), δ 3.50 (t, 2H), δ3.46-3.37 (m, 1H), δ 2.37-2.23 (m, 8H), δ 1.95-1.12 (m, 70H), δ 0.95-0.87 (m, 12H), δ 0.31 (d, 6H), δ 0.24 (s, 6H) Example 193 Synthesis of heptadecan-9-yl 10-heptyl-20-(4-hydroxybutyl)-12,12-dimethyl-9,11,13-trioxa-20-aza-12-silaoctacosan-28-oate [ka]

[0280] Heptadecan-9-yl 10-heptyl-20-(4-hydroxybutyl)-12,12-dimethyl-9,11,13-trioxa-20-aza-12-silaoctacosan-28-oate was prepared from 1-bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silanonadecane (649.92 mg, 1.311 mmol, 1.1 equiv.) and heptadecan-9-yl 8-((4-hydroxybutyl)amino)octanoate (560 mg, 0.1192 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified twice by flash column chromatography according to purification method B to give the pure product as a colorless oil (213 mg, 0.241 mmol, 20% yield). 1H NMR (500 MHz, benzene-d6) δ 5.16 (m, 1H), δ 5.00 (t, 1H), δ 3.91-3.82 (m, 1H), δ 3.76 (t, 2H), δ 3.62 (t, 2H), δ3.46-3.38 (m, 2H), δ 2.36-2.24 (m, 7H), δ 1.96-1.77 (m, 2H) δ1.71-1.12 (m, 73H), δ 0.94-0.87 (m, 12H), δ 0.28 (d, 6H); TOF MS ES + [M+H + ]:884.8111 m / z Example 194 Synthesis of 4-((6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)amino)butan-1-ol [ka]

[0281] 4-(bis(6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)amino)butan-1-ol was prepared from ((6-bromo-1(octyloxy)hexyl)oxy)dimethyl(octyl)silane (148.06 mg, 0.309 mmol, 1 equiv.) and 4-(((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)amino)butan-1-ol (150 mg (74% purity), 0.309 mmol, 1.0 equiv.) according to general procedure G. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (100 mg, 0.132 mmol, 43% yield). 1H NMR (500 MHz, benzene-d6) δ 5.53-5.38 (m, 10H), δ 4.88 (dt, 1H), δ 3.78-3.73 (m, 1H), δ 3.61 (t, 2H), δ 3.41-3.35 (m, 1H), δ2.92-2.83 (m, 8H), δ 2.35-2.34 (q, 4H), δ 2.25 (t, 2H), δ2.10-1.99 (m, 4H), δ 1.88-1.19 (m, 40H), δ 0.95-0.89 (m, 9H), δ0.76-0.72 (m, 2H), δ 0.25 (d, 6H); TOF MS ES + [M+H + ]:758.6862 m / z Example 195 Synthesis of 13-heptyl-5-((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)-15,15-dimethyl-12,14-dioxa-5-aza-15-silatricosan-1-ol [ka]

[0282] 13-Heptyl-5-((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)-15,15-dimethyl-12,14-dioxa-5-aza-15-silatricosan-1-ol was prepared according to general procedure G from ((1-((6-bromohexyl)oxy)octyl)oxy)dimethyl(octyl)silane (148.06 mg, 0.309 mmol, 1.0 equiv.) and 4-(((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)amino)butan-1-ol (150 mg (74% pure), 0.309 mmol, 1.0 equiv.). The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (234 mg, 0.207 mmol, 67% yield). 1H NMR (500 MHz, benzene-d6) δ 5.60-5.39 (m, 10H), δ4.89-4.85 (m, 1H), δ 3.78-3.73 (m, 1H), δ 3.61 (t, 2H), δ3.40-3.31 (m, 1H), δ 2.91-2.81 (m, 8H), δ 2.32 (m, 4H), δ 2.26 (t, 2H), δ 2.10-2.01 (m, 4H), δ 1.88-1.19 (m, 40H), δ 0.96-0.89 (m, 9H), δ0.78-0.71 (m, 2H), δ 0.24 (t, 6H); TOF MS ES + [M+H + ]:758.6857 m / z Example 196 Synthesis of 5-((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)-13,13-dimethyl-11-(octyloxy)-12,14-dioxa-5-aza-13-siladocosan-1-ol [ka]

[0283] 5-((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)-13,13-dimethyl-11-(octyloxy)-12,14-dioxa-5-aza-13-siladocosane-1-ol was prepared from 12-(5-bromopentyl)-10,10-dimethyl-9,11,13-trioxa-10-silahenicosane (227.43 mg, 0.459 mmol, 1.1 equiv.) and 4-(((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)amino)butan-1-ol (150 mg, 0.417 mmol, 1 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (145 mg, 0.187 mmol, 45% yield). 1H NMR (500 MHz, benzene-d6) δ 5.53-5.39 (m, 10H), δ 5.00 (m, 1H), δ 3.89-3.87 (m, 1H), δ 3.77 (t, 2H), δ 3.61 (t, 2H), δ3.45-3.35 (m, 1H), δ 2.92-2.80 (m, 8H), δ 2.42-2.29 (m, 6H), δ2.10-1.99 (m, 4H), δ 1.95-1.77 (m, 2H), δ 1.71-1.20 (m, 38H), δ0.95-0.87 (m, 9H), δ 0.28 (d 6H); TOF MS ES + [M+H + ]:774.6801 m / z Example 197 Synthesis of 13-heptyl-5-((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)-15,15-dimethyl-12,14,16-trioxa-5-aza-15-silatetracosan-1-ol [ka]

[0284] 13-Heptyl-5-((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)-15,15-dimethyl-12,14,16-trioxa-5-aza-15-silatetracosan-1-ol was prepared from 1-bromo-8-heptyl-10,10-dimethyl-7,9,11-trioxa-10-silanonadecane (206.76 mg, 0.417 mmol, 1.0 equiv.) and 4-(((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)amino)butan-1-ol (150 mg, 0.417 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (155 mg, 0.200 mmol, 48% yield). 1H NMR (500 MHz, benzene-d6) δ 5.50-5.39 (m, 10H), δ 5.00 (t, 1H), δ 3.89-3.83 (m, 1H), δ 3.76 (t, 2H), δ 3.61 (t, 2H), δ3.44-3.37 (m, 1H), δ 2.92-2.83 (m, 8H), δ 2.34-2.31 (m, 4H), δ 2.25 (t, 2H), δ 2.10-1.99 (m, 4H), δ 1.94-1.78 (m, 2H), δ 1.72-1.17 (m, 38H), δ0.95-0.87 (m, 9H), δ 0.27 (d, 6H); TOF MS ES + [M+H + ]:774.6811 m / z Example 198 Synthesis of 4-(((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)hexyl)amino)butan-1-ol [ka]

[0285] 4-(((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)hexyl)amino)butan-1-ol was converted to 1-((6-bromo-1-octyloxy) The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (187 mg, 0.225 mmol, 54% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.52-5.38 (m, 10H), δ 5.00 (t, 1H), δ 3.89-3.83 (m, 1H), δ 3.61 (t, 2H), δ 3.44-3.37 (m, 1H), δ2.92-2.80 (m, 8H), δ 2.36-2.29 (m, 4H), δ 2.25 (t, 2H), δ2.09-1.99 (m, 4H), δ 1.94-1.77 (m, 2H), δ 1.72-1.19 (m, 38H), δ0.95-0.88 (m, 9H), δ 0.69-0.65 (m, 2H), δ 0.26 (d, 6H), δ 0.21 (s, 6H); TOF MS ES + [M+H + ]:832.7034 m / z Example 199 Synthesis of 13-heptyl-5-((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)-15,15,17,17-tetramethyl-12,14,16-trioxa-5-aza-15,17-disilapentacosan-1-ol [ka]

[0286] 13-Heptyl-5-((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)-15,15,17,17-tetramethyl-12,14,16-trioxa-5-aza-15,17-disilapentacosan-1-ol can be prepared according to general procedure K from 1-((1-((6-bromohexyl)oxy)oxy)- The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (180 mg, 0.216 mmol, 52% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.55-5.40 (m, 10H), δ 5.01 (t, 1H), δ 3.93-3.81 (m, 1H), δ 3.61 (t, 2H), δ 3.45-3.37 (m, 1H), δ2.92-2.83 (m, 8H), δ 2.37-2.17 (m, 6H), δ 2.11-1.98 (m, 4H), δ1.95-1.75 (m, 2H), δ 1.73-1.18 (m, 38H), δ 0.96-0.88 (m, 9H), δ0.70-0.65 (m, 2H), δ 0.29 (d, 6H), δ 0.22 (s, 6H); TOF MS ES + [M+H + ]:832.7026 m / z Example 200 Synthesis of 4-(((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)hexyl)amino)butan-1-ol [ka]

[0287] 4-(((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)hexyl)amino)butan-1-ol was prepared according to general procedure J from 4-((6-(octyloxy)-6-( Prepared from (1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)hexyl)amino)butan-1-ol (126 mg, 0.218 mmol, 1.0 equiv.) and (5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaenal (62.44 mg, 0.218 mmol, 1.0 equiv.). The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (50 mg, 0.059 mmol, 27% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.53-5.41 (m, 10H), δ 5.01 (t, 1H), δ 3.93-3.85 (m, 1H), δ 3.76 (t, 2H) δ 3.62 (t, 2H), δ3.47-3.37 (m, 1H), δ 2.92-2.82 (m, 8H), δ 2.36-2.32 (m, 4H), δ 2.26 (t, 2H) δ 2.10-1.99 (m, 4H), δ 1.95-1.79 (m, 2H), δ 1.72-1.20 (m, 38H), δ0.95-0.89 (m, 9H), δ 0.31 (d, 6H), δ 0.25 (s, 6H); TOF MS ES + [M+H + ]:848.6975 m / z Example 201 Synthesis of 13-heptyl-5-((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)-15,15,17,17-tetramethyl-12,14,16,18-tetraoxa-5-aza-15,17-disilahexacosan-1-ol [ka]

[0288] 13-Heptyl-5-((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)-15,15,17,17-tetramethyl-12,14,16,18-tetraoxa-5-aza-15,17-disilahexacosan-1-ol was prepared according to general procedure K with 1-((1-((6-bromohexyl)oxy)octyl)-2-methyl-2-(2-hydroxybenzoyl)-1-propanol. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (125 mg, 0.147 mmol, 44% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.53-5.39 (m, 10H), δ 5.04 (dt, 1H), δ 3.90-3.84 (m, 1H), δ 3.76 (t, 2H) δ 3.61 (t, 2H), δ3.46-3.34 (m, 1H), δ 2.93-2.81 (m, 8H), δ 2.43-2.30 (m, 4H), δ 2.25 (t, 2H) δ 2.11-2.00 (m, 4H), δ 1.96-1.80 (m, 2H), δ 1.72-1.19 (m, 38H), δ0.95-0.87 (m, 9H), δ 0.31 (d, 6H), δ 0.24 (s, 6H); TOF MS ES + [M+H+ ]:848.6992 m / z Example 202 Synthesis of 16-hexyl-5-((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)-13,13-dimethyl-11-(octyloxy)-12,14-dioxa-5-aza-13-silatetracosan-1-ol [ka]

[0289] 16-Hexyl-5-((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)-13,13-dimethyl-11-(octyloxy)-12,14-dioxa-5-aza-13-silatetracosan-1-ol can be prepared according to general procedure K from 10-(5-bromopentyl)-15-hexyl-12 The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (185 mg, 0.209 mmol, 56% yield). 1H NMR (500 MHz, benzene-d6) δ 5.53-5.39 (m, 10H), δ 5.02 (t, 1H), δ3.92-3.86 (m, 1H), δ 3.76 (d, 2H), δ 3.61 (t, 2H), δ3.48-3.38 (m, 1H), δ 2.93-2.82 (m, 8H), δ 2.37-2.30 (m, 4H), δ 2.26 (t, 2H), δ 2.10-1.99 (m, 4H), δ 1.96-1.79 (m, 2H), δ 1.73-1.23 (m, 51H), δ0.96-0.89 (m, 12H), δ 0.30 (d, 6H); TOF MS ES + [M+H + ]:886.8077 m / z Example 203 Synthesis of 13-heptyl-18-hexyl-5-((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)-15,15-dimethyl-12,14,16-trioxa-5-aza-15-silahexacosan-1-ol [ka]

[0290] 13-Heptyl-18-hexyl-5-((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)-15,15-dimethyl-12,14,16-trioxa-5-aza-15-silahexacosan-1-ol was prepared according to general procedure K from 1-bromo-8-heptyl-13-hexyl-10,10 The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (197 mg, 0.222 mmol, 61% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.53-5.39 (m, 10H), δ 5.02 (t, 1H), δ3.90-3.85 (m, 1H), δ 3.75 (d, 2H), δ 3.61 (t, 2H), δ3.46-3.37 (m, 1H), δ 2.93-2.82 (m, 8H), δ 2.35-2.30 (m, 4H), δ 2.25 (t, 2H), δ 2.10-1.99 (m, 4H), δ 1.97-1.80 (m, 2H), δ 1.71-1.24 (m, 51H), δ0.95-0.89 (m, 12H), δ 0.30 (d, 6H); TOF MS ES + [M+H + ]:886.8049 m / z Example 204 Synthesis of 14-heptyl-5-((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)-12,12-dimethyl-13,15-dioxa-5-aza-12-silatricosan-1-ol [ka]

[0291] 14-Heptyl-5-((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)-12,12-dimethyl-13,15-dioxa-5-aza-12-silatricosan-1-ol was prepared from (6-bromohexyl)dimethyl((1-(octyloxy)octyl)oxy)silane (198.08 mg, 0.413 mmol, 1.1 equiv.) and 4-(((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)amino)butan-1-ol (135.00 mg, 0.375 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (159 mg, 0.210 mmol, 56% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.53-5.39 (m, 10H), δ 4.88 (t, 1H), δ3.79-3.73 (m, 1H), δ 3.62 (t, 2H), δ 3.41-3.35 (m, 1H), δ2.93-2.81 (m, 8H), δ 2.38-2.32 (m, 4H), δ 2.27 (t, 2H), δ2.13-1.99 (m, 4H), δ 1.88-1.22 (m, 40H), δ 0.96-0.87 (m, 9H), δ0.75-0.71 (m, 2H), δ 0.25 (d, 6H); TOF MS ES + [M+H + ]:758.6862 m / z Example 205 Synthesis of 15-heptyl-5-((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)-13,13-dimethyl-12,14,16-trioxa-5-aza-13-silatetracosan-1-ol [ka]

[0292] 15-Heptyl-5-((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)-13,13-dimethyl-12,14,16-trioxa-5-aza-13-silatetracosan-1-ol was prepared from 1-bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silanonadecane (227.43 mg, 0.459 mmol, 1.1 equiv.) and 4-(((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)amino)butan-1-ol (150 mg, 0.417 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (155 mg, 0.200 mmol, 48% yield). 1H NMR (500 MHz, benzene-d6) δ 5.53-5.39 (m, 10H), δ 5.00 (t, 1H), δ 3.89-3.84 (m, 1H), δ 3.75 (t, 2H), δ 3.61 (t, 2H), δ3.45-3.35 (m, 1H), δ 2.93-2.81 (m, 8H), δ 2.34-2.30 (m, 4H), δ 2.25 (t, 2H), δ 2.11-1.99 (m, 4H), δ 1.95-1.78 (m, 2H), δ 1.71-1.20 (m, 38H), δ0.95-0.87 (m, 9H), δ 0.28 (d, 6H); TOF MS ES + [M+H + ]:774.6809 m / z Example 206 Synthesis of 15-heptyl-5-(4-hydroxybutyl)-13,13-dimethyl-12,14,16-trioxa-5-aza-13-silatetracosyl (9Z,12Z)-octadeca-9,12-dienoate [ka]

[0293] 15-Heptyl-5-(4-hydroxybutyl)-13,13-dimethyl-12,14,16-trioxa-5-aza-13-silatetracosyl (9Z,12Z)-octadeca-9,12-dienoate was prepared from 1-bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silanonadecane (501.9 mg, 1.013 mmol, 1.1 equiv.) and 4-((4-hydroxybutyl)amino)butyl (9Z,12Z)-octadeca-9,12-dienoate (390.0 mg, 0.921 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (72 mg, 0.086 mmol, 9% yield). 1H NMR (500 MHz, benzene-d6) δ 5.54-5.43 (m, 4H), δ 4.99 (dd, 1H), δ 4.06 (t, 2H), δ 3.88-3.83 (m, 1H), δ 3.76 (t, 2H), δ 3.58 (t, 2H), δ 3.44-3.39 (m, 1H), δ 2.88 (t, 2H), δ2.29-2.16 (m, 7H), δ 2.10-2.04 (m, 4H), δ 1.94-1.77 (m, 2H), δ1.68-1.14 (m, 56H), δ 0.91-0.87 (m, 9H), δ 0.28 (d, 6H); TOF MS ES + [M+H + ]:838.7358 m / z Example 207 Synthesis of 5-(3-((8Z,11Z)-heptadeca-8,11-dien-1-yl)-5,5-dimethyl-2,4,6-trioxa-5-siladecane-10-yl)-15-heptyl-13,13-dimethyl-12,14,16-trioxa-5-aza-13-silatetracosan-1-ol [ka]

[0294] 5-(3-((8Z,11Z)-heptadeca-8,11-dien-1-yl)-5,5-dimethyl-2,4,6-trioxa-5-siladecane-10-yl)-15-heptyl-13,13-dimethyl-12,14,16-trioxa-5-aza-13-silatetracosan-1-ol was prepared according to general procedure K from 10-bromo-3-((8Z,11Z)-heptadeca-8,11-dien-1-yl)-5,5-dimethyl-2,4,6-trioxa-5-siladecane-10-yl)-15-heptyl-13,13-dimethyl-12,14,16-trioxa-5-aza-13-silatetracosan-1-ol. It was prepared from (butadeca-8,11-dien-1-yl)-5,5-dimethyl-2,4,6-trioxa-5-siladecane (176.6 mg, 0.349 mmol, 1.1 equiv.) and 15-heptyl-13,13-dimethyl-12,14,16-trioxa-5-aza-13-silatetracosan-1-ol (160 mg, 0.317 mmol, 1.0 equiv.). The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (42 mg, 0.045 mmol, 14% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.55-5.44 (m, 4H), δ 5.01 (dd, 1H), δ 4.81 (dd, 1H), δ3.93-3-84 (m, 1H), δ 3.79-3.72 (m, 4H), δ 3.61 (t, 2H), δ 3.45-3.38 (m, 1H), δ 3.32 (s, 3H), δ 2.90 (t, 2H), δ 2.45-2.24 (m, 6H), δ 2.12-2.06 (m, 4H), δ 1.96-1.75 (m, 4H), δ1.71-1.20 (m, 58H), δ 0.93-0.88 (m, 9H), δ 0.30 (d, 6H), δ 0.25 (d, 6H); TOF MS ES + [M+H + ]:928.7825 m / z Example 208 Synthesis of 5-(4-hydroxybutyl)-13,13,15-trimethyl-12,14,16-trioxa-5-aza-13-silahexacosyl (9Z,12Z)-octadeca-9,12-dienoate [ka]

[0295] 5-(4-Hydroxybutyl)-13,13,15-trimethyl-12,14,16-trioxa-5-aza-13-silahexacosyl (9Z,12Z)-octadeca-9,12-dienoate was prepared from 1-bromo-8,8,10-trimethyl-7,9,11-trioxa-8-silahenicosane (836.9 mg, 1.713 mmol, 1.1 equiv.) and 4-((4-hydroxybutyl)amino)butyl (9Z,12Z)-octadeca-9,12-dienoate (660.0 mg, 1.558 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (50 mg, 0.064 mmol, 4% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.55-5.45 (m, 4H), δ 5.09 (q, 1H), δ 4.07 (t, 2H), δ3.85-3.79 (m, 1H), δ 3.73 (t, 2H), δ 3.58 (t, 2H), δ 3.40-3.34 (m, 1H), δ 2.89 (t, 2H), δ2.29-2.17 (m, 8H), δ 2.11-2.05 (m, 4H), δ 1.70-1.15 (m, 51H), δ0.94-0.80 (m, 6H), δ 0.24 (d, 6H); LC ESI MS [M+H + ]:782.670 m / z Example 209 Synthesis of undecyl 9-heptyl-20-(2-hydroxyethyl)-7,7-dimethyl-8,10-dioxa-20-aza-7-silahexacosane-26-oate [ka]

[0296] Undecyl 9-heptyl-20-(2-hydroxyethyl)-7,7-dimethyl-8,10-dioxa-20-aza-7-silahexacosane-26-oate was prepared from ((1-((9-bromononyl)oxy)octyl)oxy)(hexyl)dimethylsilane (206.00 mg, 0.417 mmol, 1.1 equiv.) and undecyl 6-((2-hydroxyethyl)amino)hexanoate (125.00 mg, 0.379 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified twice by flash column chromatography according to purification method A to give the pure product as a colorless oil (201 mg, 0.2708 mmol, 71% yield). 1 H NMR (500 MHz, benzene-d6) δ 4.89 (dt, 1H), δ 4.08 (t, 2H), δ 3.80-3.74 (m, 1H), δ 3.49 (t, 2H), δ 3.42-3.37 (m, 1H), δ 2.34 (t, TOF MS ES + [M+H + ]:742.6735 m / z Example 210 Synthesis of undecyl 6-((10-((hexyldimethylsilyl)oxy)-10-(octyloxy)decyl)(2-hydroxyethyl)amino)hexanoate [ka]

[0297] Undecyl 6-((10-((hexyldimethylsilyl)oxy)-10-(octyloxy)decyl)(2-hydroxyethyl)amino)hexanoate was prepared from ((10-bromo-1-(octyloxy)decyl)oxy)(hexyl)dimethylsilane (211.85 mg, 0.417 mmol, 1.1 equiv.) and undecyl 6-((2-hydroxyethyl)amino)hexanoate (125.00 mg, 0.379 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified twice by flash column chromatography according to purification method A to give the pure product as a colorless oil (200 mg, 0.264 mmol, 70% yield). 1 H NMR (500 MHz, benzene-d6) δ 4.89 (dt, 1H), δ 4.08 (t, 2H), δ 3.77-3.73 (m, 1H), δ 3.49 (t, 2H), δ 3.39-3.36 (m, 1H), δ 2.34 (t, TOF MS ES + [M+H + ]:756.6902 m / z Example 211 Synthesis of undecyl 17-heptyl-7-(4-hydroxybutyl)-15,15-dimethyl-14,16,18-trioxa-7-aza-15-silahexacosanoate [ka]

[0298] Undecyl 17-heptyl-7-(4-hydroxybutyl)-15,15-dimethyl-14,16,18-trioxa-7-aza-15-silahexacosanoate was prepared from 1-bromo-10-heptyl-8,8-dimethyl-7,9,11-trioxa-8-silanonadecane (485.15 mg, 0.979 mmol, 1.0 equiv.) and undecyl 6-((4-hydroxybutyl)amino)hexanoate (350.0 mg, 0.979 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified twice by flash column chromatography according to purification method B to give the pure product as a colorless oil (179 mg, 0.231 mmol, 24% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.11 (dd, 1H), δ 4.18 (t, 2H), δ 3.87 (t, 2H), δ 3.71 (t, 2H), δ 3.55-3.46 (m, 1H), δ2.41-2.29 (m, 7H), δ 2.06-1.88 (m, 2H), δ 1.80-1.28 (m, 59H), δ1.04-0.99 (m, 9H), δ 0.39 (d, 6H); TOF MS ES + [M+H + ]:772.6857 m / z Example 212 Synthesis of undecyl 6-((6-((dimethyl((oxacyclohexadecan-2-yl)oxy)silyl)oxy)hexyl)(4-hydroxybutyl)amino)hexanoate [ka]

[0299] Undecyl 6-((6-((dimethyl((oxacyclohexadecan-2-yl)oxy)silyl)oxy)hexyl)(4-hydroxybutyl)amino)hexanoate was prepared from ((6-bromohexyl)oxy)dimethyl((oxacyclohexadecan-2-yl)oxy)silane (1.032 g, 2.153 mmol, 1.1 equiv.) and undecyl 6-((4-hydroxybutyl)amino)hexanoate (700.0 mg, 1.958 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified twice by flash column chromatography according to purification method B to give the pure product as a colorless oil (250 mg, 0.331 mmol, 21% yield). 1 H NMR (500 MHz, benzene-d6) δ 4.95-4.92 (dd, 1H), δ 4.06 (t, 2H), δ 3.95-3.90 (m, 1H), δ 3.73 (t, 2H), δ 3.60 (t, 2H), δ 3.40 (t, 1H), δ 3.29 (t, 1H), δ2.30-2.17 (m, 7H), δ1.94-1.87 (m, 1H), δ 1.84-1.80(m, 1H), δ 1.74-1.15 (m, 60H), δ 0.93-0.90 (m, 3H), δ 0.24 (d, 6H); TOF MS ES + [M+H + ]:756.6555 m / z Example 213 Synthesis of undecyl 7-(4-hydroxybutyl)-15,15,17-trimethyl-14,16,18-trioxa-7-aza-15-silaoctacosanoate [ka]

[0300] Undecyl 7-(4-hydroxybutyl)-15,15,17-trimethyl-14,16,18-trioxa-7-aza-15-silaoctacosanoate was prepared from 1-bromo-8,8,10-trimethyl-7,9,11-trioxa-8-silahenicosane (1250.0 mg, 2.842 mmol, 1.1 equiv.) and undecyl 6-((4-hydroxybutyl)amino)hexanoate (960.0 mg, 2.583 mmol, 1.0 equiv.) according to general procedure K. The crude product was purified twice by flash column chromatography according to purification method B to give the pure product as a colorless oil (435 mg, 0.607 mmol, 23% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.09 (q, 1H), δ 4.07 (t, 2H), δ 3.85-3.76 (m, 1H), δ 3.72 (t, 2H), δ 3.61 (t, 2H), δ3.40-3.33 (m, 1H), δ 2.31-2.17 (m, 8H), δ 1.70-1.15 (m, 55H), δ0.93-0.89 (m, 6H), δ 0.25 (d, 6H); TOF MS ES + [M+H + ]:716.6218 m / z Example 214 Synthesis of 4-((6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentyl)amino)butan-1-ol [ka]

[0301] 4-((6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentyl)amino)butan-1-ol can be converted to 4-((6-((dimethyl(octyl)silyl)oxy)-6-(octyloxy)hexyl)((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentyl)amino)butan-1-ol according to general procedure J. (4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanal (115.17 mg, 0.307 mmol, 1.0 equiv.). The crude product was purified twice by flash column chromatography according to purification methods A and B to give the pure product as a colorless oil (120 mg, 0.142 mmol, 46% yield). 1 H NMR (500 MHz, benzene-d6) δ 4.88 (dt, 1H), δ4.78-4.70 (m, 1H), δ 3.79-3.73 (m, 1H), δ 3.64 (t, 2H), δ 3.43 (s, 3H), δ 3.43-3.36 (m, TOF MS ES + [M+H + ]:846.7743 m / z Example 215 Synthesis of 13-heptyl-5-((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentyl)-15,15-dimethyl-12,14-dioxa-5-aza-15-silatricosan-1-ol [ka]

[0302] 13-Heptyl-5-((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentyl)-15,15-dimethyl-12,14-dioxa-5-aza-15-silatricosan-1-ol was prepared according to general procedure J from 13-heptyl-15,15-dimethyl-12, Prepared from 14-dioxa-5-aza-15-silatricosan-1-ol (150.00 mg, 0.307 mmol, 1.0 equiv.) and (4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentanal (115.17 mg, 0.307 mmol, 1.0 equiv.). The crude product was purified twice by flash column chromatography according to purification methods A and B to give the pure product as a colorless oil (163 mg, 0.193 mmol, 63% yield). 1 H NMR (500 MHz, benzene-d6) δ 4.87 (dt, 1H), δ4.77-4.69 (m, 1H), δ 3.77-3.72 (m, 1H), δ 3.64 (t, 2H), δ 3.43 (s, 3H), δ 3.39-3.35 (m, 1H), δ 2.43-2.30 (m, 6H), δ 1.96-0.70 (m, 78H), δ 0.61 (s, 3H), δ 0.25 (d, 6H); + [M+H + ]:846.7725 m / z Example 216 Synthesis of 5-((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentyl)-13,13-dimethyl-11-(octyloxy)-12,14-dioxa-5-aza-13-siladocosan-1-ol [ka]

[0303] 5-((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentyl)-13,13-dimethyl-11-(octyloxy)-12,14-dioxa-5-aza-13-siladocosan-1-ol was prepared according to general procedure K from 12-(5-bromopentyl)-10,10-dimethyl-9, Prepared from 11,13-trioxa-10-silahenicosane (113.25 mg, 0.228 mmol, 1.1 equiv.) and 4-(((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentyl)amino)butan-1-ol (93.00 mg, 0.208 mmol, 1.0 equiv.). The crude product was purified twice by flash column chromatography according to purification method A to give the pure product as a colorless oil (58 mg, 0.067 mmol, 32% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.00 (dt, 1H), δ4.78-4.70 (m, 1H), δ 3.89-3.84 (m, 1H), δ 3.77 (t, 2H), δ 3.64 (t, 2H), δ 3.45-3.43 (m, TOF MS ES + [M+H + ]:862.7687 m / z Example 217 Synthesis of 13-heptyl-5-((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentyl)-15,15-dimethyl-12,14,16-trioxa-5-aza-15-silatetracosan-1-ol [ka]

[0304] 13-Heptyl-5-((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentyl)-15,15-dimethyl-12,14,16-trioxa-5-aza-15-silatetracosan-1-ol was prepared according to general procedure K from 1-bromo-8-heptyl-10,10-dimethyl-7 The crude product was prepared from 9,11-trioxa-10-silanonadecane (113.25 mg, 0.228 mmol, 1.1 equiv.) and 4-((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentyl)amino)butan-1-ol (93.00 mg, 0.208 mmol, 1.0 equiv.). The crude product was purified twice by flash column chromatography according to purification method A to give the pure product as a colorless oil (39 mg, 0.045 mmol, 22% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.00 (dt, 1H), δ4.78-4.68 (m, 1H), δ 3.88-3.83 (m, 1H), δ 3.77 (t, 2H), δ3.66-3.61 (m, 2H), δ 3.46-3.39 (m, 4H), δ 2.45-2.25 (m, 6H), δ1.97-0.75 (m, 76H), δ 0.61 (s, 3H), δ 0.28 (d, 6H); TOF MS ES + [M+H + ]:862.7692 m / z Example 218 Synthesis of 4-(((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentyl)(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-octyldisiloxaneyl)oxy)hexyl)amino)butan-1-ol [ka]

[0305] 4-(((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentyl)(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-octyldisiloxanayl)oxy)hexyl)amino)butan-1-ol was prepared according to general procedure K with 1-((6-bromo-1-(octyloxy)hexyl)amino)butan-1-ol. The crude product was prepared from 4-(((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentyl)amino)butan-1-ol (93.00 mg, 0.208 mmol, 1.0 equiv.) and 4-(((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentyl)amino)butan-1-ol (93.00 mg, 0.208 mmol, 1.0 equiv.). The crude product was purified twice by flash column chromatography according to purification method A to give the pure product as a colorless oil (107 mg, 0.116 mmol, 56% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.01 (dt, 1H), δ4.78-4.70 (m, 1H), δ 3.89-3.82 (m, 1H), δ 3.64 (t, 2H), δ3.48-3.39 (m, 4H), δ 2.45-2.29 (m, 6H), δ 1.97-0.70 (m, 78H), δ 0.61 (s, 3H), δ 0.27 (d, 6H), δ 0.22 (s, 6H); TOF MS ES + [M+H + ]:920.7921 m / z Example 219 Synthesis of 13-heptyl-5-((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentyl)-15,15,17,17-tetramethyl-12,14,16-trioxa-5-aza-15,17-disilapentacosan-1-ol [ka]

[0306] 13-Heptyl-5-((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentyl)-15,15,17,17-tetramethyl-12,14,16-trioxa-5-aza-15,17-disilapentacosan-1-ol was prepared according to general procedure K from 1-((1-((6-bromohexyl)oxy)octyl)- The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (65 mg, 0.071 mmol, 34% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.01 (dt, 1H), δ4.78-4.70 (m, 1H), δ 3.88-3.83 (m, 1H), δ 3.64 (t, 2H), δ3.43-3.38 (m, 4H), δ 2.41-2.29 (m, 6H), δ 1.97-0.70 (m, 78H), δ 0.61 (s, 3H), δ 0.26 (d, 6H), δ 0.21 (s, 6H); TOF MS ES + [M+H + ]:920.7930 m / z Example 220 Synthesis of 4-(((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentyl)(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)hexyl)amino)butan-1-ol [ka]

[0307] 4-(((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentyl)(6-(octyloxy)-6-((1,1,3,3-tetramethyl-3-(octyloxy)disiloxaneyl)oxy)hexyl)amino)butan-1-ol was prepared according to general procedure J from 4-((6-(octyloxy)-6-((1,1 This crude product was prepared from (4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanal (87.42 mg, 0.209 mmol, 1.0 equiv.) and (4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanal (87.42 mg, 0.209 mmol, 1.0 equiv.). The crude product was purified twice by flash column chromatography according to purification method A to give the pure product as a colorless oil (50 mg, 0.053 mmol, 25% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.03 (t, 1H), δ4.77-4.70 (m, 1H), δ 3.92-3.85 (m, 1H), δ 3.76 (t, 2H), δ 3.63 (t, 2H), δ 3.46-3.37 (m, TOF MS ES+ [M+H + ]:936.7874 m / z Example 221 Synthesis of 13-heptyl-5-((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentyl)-15,15,17,17-tetramethyl-12,14,16,18-tetraoxa-5-aza-15,17-disilahexacosan-1-ol [ka]

[0308] 13-Heptyl-5-((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentyl)-15,15,17,17-tetramethyl-12,14,16,18-tetraoxa-5-aza-15,17-disilahexacosan-1-ol was converted to 1-((1-((6-bromohexyl)oxy)octyl)- ... (4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentyl)amino)butan-1-ol (93.00 mg, 0.208 mmol, 1.0 equiv.). The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (69 mg, 0.074 mmol, 35% yield). 1H NMR (500 MHz, benzene-d6) δ 5.03 (t, 1H), δ4.78-4.70 (m, 1H), δ 3.90-3.84 (m, 1H), δ 3.76 (t, 2H), δ 3.64 (t, 2H), δ 3.47-3.37 (m, TOF MS ES + [M+H + ]:936.7881 m / z Example 222 Synthesis of 16-hexyl-5-((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentyl)-13,13-dimethyl-11-(octyloxy)-12,14-dioxa-5-aza-13-silatetracosan-1-ol [ka]

[0309] 16-Hexyl-5-((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentyl)-13,13-dimethyl-11-(octyloxy)-12,14-dioxa-5-aza-13-silatetracosan-1-ol was prepared according to general procedure K from 10-(5-bromopentyl)-15-hexyl-12,1 Prepared from 2-dimethyl-9,11,13-trioxa-12-silatricosane (194.14 mg, 0.319 mmol, 1.19 equiv.) and 4-(((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentyl)amino)butan-1-ol (120.00 mg, 0.268 mmol, 1.0 equiv.). The crude product was purified twice by flash column chromatography according to purification methods A and B to give the pure product as a colorless oil (100 mg, 0.103 mmol, 38% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.02 (t, 1H), δ 4.78-4.70 (m, 1H), δ 3.91-3.86 (m, 1H), δ 3.76 (d, 2H), δ 3.64 (t, 2H), δ3.47-3.37 (m, TOF MS ES + [M+H + ]:974.8928 m / z Example 223 Synthesis of 13-heptyl-18-hexyl-5-((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentyl)-15,15-dimethyl-12,14,16-trioxa-5-aza-15-silahexacosan-1-ol [ka]

[0310] 13-Heptyl-18-hexyl-5-((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentyl)-15,15-dimethyl-12,14,16-trioxa-5-aza-15-silahexacosan-1-ol was prepared according to general procedure K from 1-bromo-8-heptyl-13-hexyl-10,10- Prepared from dimethyl-7,9,11-trioxa-10-silahenicosane (179.21 mg, 0.295 mmol, 1.10 equiv.) and 4-(((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentyl)amino)butan-1-ol (120.00 mg, 0.268 mmol, 1.0 equiv.). The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (109 mg, 0.112 mmol, 42% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.02 (t, 1H), δ4.78-4.70 (m, 1H), δ 3.90-3.84 (m, 1H), δ 3.75 (d, 2H), δ 3.64 (t, 2H), δ 3.46-3.38 (m, TOF MS ES + [M+H + ]:974.8949 m / z Example 224 Synthesis of 14-heptyl-5-((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentyl)-12,12-dimethyl-13,15-dioxa-5-aza-12-silatricosan-1-ol [ka]

[0311] 14-Heptyl-5-((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentyl)-12,12-dimethyl-13,15-dioxa-5-aza-12-silatricosan-1-ol was prepared according to general procedure K using (6-bromohexyl)dimethyl((1-(octyl)methyl)-2-methyl-1-propanol). The crude product was purified by flash column chromatography according to purification method A to give the pure product as a colorless oil (106 mg, 0.125 mmol, 37% yield). 1 H NMR (500 MHz, benzene-d6) δ 4.88 (dt, 1H), δ4.78-4.70 (m, 1H), δ 3.79-3.73 (m, 1H), δ 3.65 (t, 2H), δ 3.43 (s, 3H), δ 3.41-3.36 (m, TOF MS ES + [M+H + ]:846.7731 m / z Example 225 Synthesis of 15-heptyl-5-((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentyl)-13,13-dimethyl-12,14,16-trioxa-5-aza-13-silatetracosan-1-ol [ka]

[0312] 15-Heptyl-5-((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentyl)-13,13-dimethyl-12,14,16-trioxa-5-aza-13-silatetracosan-1-ol was prepared according to general procedure K from 1-bromo-10-heptyl-8,8-dimethyl-7, Prepared from 9,11-trioxa-8-silanonadecane (152.21 mg, 0.307 mmol, 1.10 equiv.) and 4-(((4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentyl)amino)butan-1-ol (125.00 mg, 0.279 mmol, 1.0 equiv.). The crude product was purified twice by flash column chromatography according to purification methods A and B to give the pure product as a colorless oil (43 mg, 0.050 mmol, 18% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.00 (td, 1H), δ4.78-4.70 (m, 1H), δ 3.89-3.84 (m, 1H), δ 3.77 (t, 2H), δ 3.64 (t, 2H), δ 3.46-3.38 (m, TOF MS ES + [M+H + ]:862.7667 m / z Example 226 Synthesis of 15-heptyl-5-(4-hydroxybutyl)-13,13-dimethyl-12,14,16-trioxa-5-aza-13-silatetracosyl (4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentanoate [ka]

[0313] 15-Heptyl-5-(4-hydroxybutyl)-13,13-dimethyl-12,14,16-trioxa-5-aza-13-silatetracosyl (4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentanoate was prepared according to general procedure K from 1-bromo-10-heptyl-8,8-dimethyl-7 The crude product was prepared from 9,11-trioxa-8-silanonadecane (582.14 mg, 1.174 mmol, 1.1 equiv.) and 4-((4-hydroxybutyl)amino)butyl (4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoate (555.0 mg, 1.068 mmol, 1.0 equiv.). The crude product was purified by flash column chromatography according to purification method B to give the pure product as a colorless oil (84 mg, 0.089 mmol, 83% yield). 1 H NMR (500 MHz, benzene-d6) δ 5.01 (td, 1H), δ 4.10 (t, 2H), δ 3.90-3.84 (m, 1H), δ 3.77 (t, 2H), δ 3.59 (t, 2H), δ3.45-3.40 (m, 1H), δ 3.25 (s, 3H), δ 3.09-3.02 (m, 1H), δ2.43-2.21 (m, 8H), δ 2.00-1.20 (m, 62H), δ 1.03-0.79 (m, 16H), δ 0.60 (s, 3H), δ 0.29 (d, 6H); TOF MS ES + [M+H + ]:948.8075 m / z Example 227 Synthesis of 14-heptyl-5-(4-hydroxybutyl)-12,12-dimethyl-13,15-dioxa-5-aza-12-silatricosyl (4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentanoate [ka]

[0314] 14-Heptyl-5-(4-hydroxybutyl)-12,12-dimethyl-13,15-dioxa-5-aza-12-silatricosyl(4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-17-yl)pentanoate was prepared according to general procedure K using (6-bromohexyl)dimethyl((1-(octyl) The crude product was prepared from (4-hydroxybutyl)amino)butyl (4R)-4-((3R,10S,13R)-3-methoxy-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoate (550.0 mg, 1.058 mmol, 1.0 equiv.) according to purification method B. The crude product was purified by flash column chromatography to give the pure product as a colorless oil (250 mg, 0.268 mmol, 25% yield). 1H NMR (500 MHz, benzene-d6) δ 4.89 (td, 1H), δ 4.10 (t, 2H), δ 3.79-3.74 (m, 1H), δ 3.60 (t, 2H), δ 3.41-3.36 (m, 1H), δ 3.25 (s, 3H), δ 3.08-3.02 (m, 1H), δ 2.39-2.23 (m, 9H), δ 2.01-1.95 (m, 1H), δ1.90-1.72 (m, 8H), δ 1.59-1.13 (m, 54H), δ 1.05-0.72 (m, 16H), δ 0.60 (s, 3H), δ 0.27 (d, 6H); TOF MS ES + [M+H + ]:932.8140 m / z

[0315] Lipid nanoparticle preparation and characterization, transfection and viability studies The synthesized lipids were tested on HeLa cells for in vitro transfection efficacy and toxicity. To perform the mentioned biological tests, appropriate LNPs had to be formulated from the synthesized lipids. The formulation techniques differed between Methods A and B. The particle size, PDI, and zeta potential of the resulting LNPs were determined by dynamic light scattering (DLS). Prior to biological testing, the encapsulation efficiency (EE) of the loaded LNPs was determined using a RiboGreen RNA assay. In Method A, luciferase mRNA was transfected into the cells, whereas in Method B, GFP mRNA was transfected into the cells. In parallel with the transfection experiments, the toxicity of the investigated LNPs was determined using a resazurin assay in Method A and an MTT assay in Method B. For some lipid examples, the apparent pKa in the LNP was determined using TNS titration based on the method described in Angew Chem Int Ed Engl. 2012, 51(34), 8529-8533, doi:10.1002 / anie.201203263).

[0316] Method A LNP Formulation and Dialysis (Method A) Preparation: 1. If necessary, prepare a stock solution by dissolving a known amount of lipid powder in an appropriate solvent. The recommended solvent is ethanol, and the recommended concentration is typically in the range of 10-50 mM. Higher concentrations are preferred to allow for a range of mRNA-LNP concentrations. 2. Remove lipid stock solution from -20°C freezer. For long-term storage, use -80°C. 3. Check vials for precipitation. DOPE (CAS No. 4004-05-1) (20 mM) and DSPE-PEG (CAS No. 474922-26-4) (5 mM) may require a 5-30 minute incubation step at 37°C (with intermittent vortexing to resuspend all contents). Vials with significant precipitation (as a result of repeated freeze-thaw cycles) may not be salvageable. As a last resort, the lipids may be heated to 50°C to resuspend them; the time should be kept as short as possible to prevent oxidation or other modification or degradation processes. 4. Mix the lipids by vortexing for 2 minutes. 5. Optionally protected from light, Cool the lipid stock solution to room temperature by incubating it on the bench. Cooling the solution removes any ethanol or Avoid excessive evaporation of similar solvents. 6. Meanwhile, thaw the RNA samples (including the latest SecNLuc control) by inserting the cryopreservation tubes into room temperature aluminum blocks. 7. Prepare each LNP formulation (RNA master mix according to Table 1 below) with the same mRNA components in a new tube. The use of a master mix allows for a more rigorous comparison between lipid formulations. Divide the master mix into a number of new tubes equal to the number of samples plus controls. Each tube contains 375 μl of mRNA in 10 mM citrate (pH 4.0). 8. Prepare each LNP formulation (lipid master mix according to Table 1 below) in a new tube with the same lipid composition, except for the lipid of interest. The use of a master mix allows for a more rigorous comparison between new ionizable lipids. Divide the master mix into a number of new tubes equal to the number of samples plus controls. Each tube contains 65.5 μl of lipid master mix. 9. Add the ionizable lipid of interest to the equally divided lipid master mix. Mix well by pipetting up and down. Label the tubes according to the ionizable lipid used. 10. Power on the "L1 Formulation Machine" (L1FM) and allow it to perform a motor position calibration. [Table 1]

[0317] Rinsing and Prewetting: 11. Place a new microfluidic cartridge (COC-plastic) into the loading slot of the L1FM. 12. Load 2 ml Eppendorf tubes into the "receiving station" of the L1FM. 13. Fill one "rinse syringe" (A) with 1 ml of RNAse-free HO and the other (B) with 1 ml of 99% EtOH from the designated "cleaning" stock solutions. 14. Install the syringes in the correct orientation (install the syringe filled with HO on the left and the syringe filled with EtOH on the right). 15. Press "Button 2" (100µg) to rinse the tip, keeping the tip in place and checking the syringe movement while running the machine. 16. Restart the machine for the next formulation. 17. Discard the flow-through.

[0318] Formulation: 18. Fill a new syringe (C) with the RNA mixture previously prepared in step 6 through an 18G stainless steel blunt needle. The volume should be approximately 85% of the total formulation volume + 25 μl (dead volume). Gently tap to ensure all air bubbles are removed. 19. Pass the lipid master mix through an 18G stainless steel blunt needle to fill a new syringe (D). The volume should be approximately 35% of the total formulation volume + 25 μl (dead volume). Again, be sure to remove all air bubbles. 20. Install the syringes in the correct orientation (install Syringe A on the left and Syringe B on the right). 21. At the "receiving station" place an appropriately sized collection container (2 ml Load the tube (Eppendorf tube). 22. Hold the microfluidic chip against the back of the machine with your thumb and press "Button 1" (40 µg). L1FM pushes the entire volume from the syringe through the microfluidic mixer chip at a total flow rate of 12 ml / ml (total flow rate (TFR)) at a perfect 3:1 (mRNA aqueous solution:lipid in EtOH) ratio. 23. Remove the sample tubes from the "receiving station" and label the tubes accordingly. 24. Reset the machine to prepare for the next formulation.

[0319] Dialysis: 25. Transfer each formulation to 100 kda MWCO, SpectraPor Biotech dialysis tubing and close with the designated clamp. 26. The dialysis bag is immersed in a beaker filled with 1x PBS buffer (pH 7.4) and stirred at 230 RPM at room temperature. 27. Incubate at room temperature for 2 hours with stirring, then refresh with 1x PBS buffer (pH 7.4). 28. Refresh the buffer and incubate for an additional 2 hours at room temperature with stirring. 29. Remove the dialysis bag from the dialysis machine and extract the LNP sample with a sterile pipette tip. 30. Dilute the sample to 1 ml with sterile 1x PBS and measure the zeta potential, size and PDI using a DLS instrument.

[0320] Measurement of size and size distribution by dynamic light scattering (Method A) Turn on the DLS (Dynamic Light Scattering) instrument 30 minutes prior to use. This allows the laser to warm up and the sample station to equilibrate to the set working temperature (usually room temperature). 1. Optionally, pool individual formulations for each unique component if manufactured in large quantities in separate batches (i.e., processed in multiple dialysis cassettes). 2. Unpack the collapsible capillary cell (DTS1070) and use one sample per assembly. 3. Hold the cuvette upside down (injection port downwards) and inject 1 ml of HO into one of the ports, which will dispense the fluid through the cell and out the other port. This process is repeated with a syringe filled with 4.1 ml of air, which dries out any excess water that may have remained in the cell after flushing. 5. Rotate the cuvette so that the injection port is at the top. 6. Dilute 10 μl of the dialyzed LNP formulation in 690 μl of 1×PBS buffer (pH 7.4). 7. Use the clear syringe to add the sample to the cell, not exceeding the "Fill, Max Line" line on the cuvette. 8. Select the "Size & Zeta" option in the "Method builder" of the "ZS Explorer" software and measure the sample to determine size, PDI and zeta potential.

[0321] Encapsulation efficiency (Method A) Required solution: 1. Preparation of sample stock solution: In the top row of a 96-well plate (row A of the plate), Using a multichannel pipette, add 297 μL of TE buffer (pH 7.4) to a single well for each sample plus a single well for the PBS blank. Add 2.3 μL of sample (0.5 mg / mL) to these wells to a final volume of 300 μL. Add 3 μL of PBS to the blank wells. Mix by pipetting. This is the stock solution for each sample. The final RNA concentration of these stock solutions should be approximately 4-7 μg / mL. 3. mRNA-LNP Sample Setup: a. Add 50 μL of TE buffer (pH 7.5) to two wells directly below each sample (rows B and C of the plate). b Add 50 μL of sample stock solution from row A to wells in rows B and C (this assay is performed in duplicate; all liquid handling should be done using a multichannel pipette). c. Add 50 μL of Triton buffer to wells in rows D and E (of the plate) below each sample. dAdd 50 μL of sample stock solution from row A to wells in rows D and E. 4. Set up a RiboGreen RNA standard curve: Dilute the RNA standards to create an RNA stock solution with a final concentration of 20 μg / mL in TE buffer (pH 7.4). The final volume should be 150 μL. Set up a standard curve (in duplicate) using the RNA stock solution (20 μg / mL siRNA), TE buffer (pH 7.5), and Triton buffer according to Table 2 below. [Table 2] 5. Once the samples and standard curve have been plated, incubate the plate at 37°C for 10 minutes to dissolve the mRNA-LNPs in the presence of Triton X-100. 6. Meanwhile, prepare RiboGreen solution: Add up the total number of sample wells and standard curve wells. Add 3 to this number and multiply the total by 100. This is the total volume (μL) of RiboGreen solution needed for this assay. In a 15 mL RNAse-free Falcon tube, dilute RiboGreen reagent 1:100 in TE buffer (pH 7.5) to the calculated total volume. 7. Add RiboGreen solution and read samples: Remove the 96-well plate from the 37°C incubator and allow to cool to room temperature, as RiboGreen binding is slightly temperature dependent. Add 100 μL of RiboGreen solution to each well. Pop any air bubbles with a needle. Read using a fluorescent plate reader (excitation=480, emission=525). 8. Sample analysis: Use the data generated by the RiboGreen standard curve to calculate the concentration of mRNA.

[0322] Transfection efficiency with luciferase-mRNA (Method A) Control transfection preparation: 1. Prepare mRNA solution by adding 100 ng of mRNA (SecNLuc, #P009024, RiboPro) to 5 μl of Opti-MEM. a. Double the number of wells to include different concentrations and add 10% extra. b. The standard settings we use are 100ng-50ng-10ng mRNA / well (triplicate), which requires 528ng of mRNA (including a 10% excess).

[0323] Transfection: 2. (If applicable) Prepare different concentrations (e.g. 100 / 50 / 10 ng) in Opti-MEM. 3. Add 10 μl to each well and mix carefully by pipetting. 4. Mix by swirling the plate horizontally at moderate speed, reversing direction three times.

[0324] 5. Incubate for 24 hours (incubator). Nano-Glo assay Background: This protocol was adapted to measure luciferase activity for secreted NanoLuc and is based on the protocol by Promega (Nano-Glo® Luciferase Assay System #N1110-1150). The protocol is designed for 384-well plates, but volumes can be modified to fit other plates.

[0325] procedure: 1. Cells (HeLa) were plated in 96-well plates and grown to 80% confluence. Transfect with SecNanoLuc mRNA and incubate for the desired period (24 h). 2. After incubation, the translated protein accumulates in the medium. Transfer the medium to a new plate or tube. 3. Transfer 12 μl of each sample to a black-walled, clear-bottom 384-well plate. a. Black-walled plates are important to prevent shine-through of luminescence from other wells; alternatively, multiple wells may be left empty between samples. 4. Set up the plate reader. 5. Prepare the desired amount of Nano-Glo® Luciferase Assay Reagent by combining one volume of Nano-Glo® Luciferase Assay Substrate with 50 volumes of Nano-Glo® Luciferase Assay Buffer. a. Composition: 100 mM MES (pH 6), 1 mM EDTA, 0.5% NP-50, 150 mM KCl, 1 mM DTT, 35 mM thiourea. b. Prior to use, briefly spin the tube containing the substrate in a microcentrifuge. 6. Add 12 μl of Nano-Glo® Luciferase Assay Reagent per well (by pipetting) and mix. Wait approximately 3 minutes before measuring the luminescence. The luminescence intensity gradually decays, and the half-life of the signal is approximately 120 minutes at room temperature. 7. Measure luminescence in a plate reader using luciferase standard protocol (this includes mixing the samples in the plate reader).

[0326] Note Thaw Nano-Glo® Luciferase Assay Buffer to room temperature, but do not exceed 25° C. at any time during this procedure.

[0327] Assessment of cell viability by resazurin assay (Method A) Background: This protocol is used to determine cellular metabolic activity as a measure of cell viability after exposure to potentially toxic substances. Resazurin is converted in the mitochondria by reduction to resorufin, which has much higher fluorescence at approximately 600 nm compared to unconverted resazurin. Lower conversion amounts / conversion rates correlate with a decrease in cellular metabolism and, indirectly, with cell death and toxicity. Careful interpretation of readings is required, as a 50% decrease in resazurin conversion rate could mean a 50% decrease in cellular metabolism for 100% viable cells, or 50% cell death, or any combination in between.

[0328] procedure: 1. Prepare a 0.25 mg / ml stock solution of resazurin in fresh cell culture medium. Resazurin auto-reduces over time in solution, especially in culture medium, so a fresh stock should be prepared every 2-3 days. The stock solution should be stored at 4°C and protected from light. For HeLa cells, use DMEM / F12 with 10% FCS. 2. Dilute the stock solution 10-fold in fresh cell culture medium to 0.025 mg / ml and it is ready to be applied to the cells. For HeLa cells, use DMEM / F12 with 10% FCS. 3. Harvest the 96-well plate and replace the cell culture spent medium with 100 μl / well of resazurin solution. Add some resazurin solution to wells without cells for background measurement. 4. Incubate in an incubator at 37°C, 5% CO2, 95% RH for 50 minutes. 5. Transfer the resazurin solution to a new 96- or 384-well plate. 6. Measure on a plate reader using standard settings (PTM low / OD-1.0) at 540 / 25 nm (excitation) and 610 / 40 nm (emission). 7. Subtract the average background measurement from all samples. The average of the negative controls (wells receiving only OptiMEM during transfection) is set to 100% and all values are expressed as a percentage of control activity.

[0329] Typically, lower levels of treatment indicate increased metabolic activity, but for toxic substances, a sigmoidal curve can be obtained at toxic concentrations, with lower activity indicating greater toxicity.

[0330] Method B LNP Formulation (Method B) Required solution: 0.33ug / uL mRNA solution (RiboPro, commercially available mRNA, eGFP with Cap1) in DEPC-treated water 0.04ug / uL mRNA solution (RiboPro, commercial mRNA, eGFP with Cap1) in DEPC-treated water [Table 3] MEM (Sigma, Catalog No. M5650-500mL) Diluent: 10 mL of MEM + 0.036 mL of ethanol Lipofectamine solution (Thermofisher / Invitrogen, catalog number 11668-019, 1 mg / mL solution)

[0331] procedure: 1. Negative control: a) Place 360 uL of dilution into an Eppendorf. 2. Test lipid formulations: In a 1.5 mL Eppendorf: a) Place 2.9 uL of 0.33 ug / uL mRNA solution into an Eppendorf tube. b) Add 1.94 μL of the supplied test lipid solution in ethanol and mix immediately by pipetting up and down several times (pump the solution up and down several times before transferring to saturate the pipette tip with ethanol vapor). c) Incubate for 15 minutes. d) Add 536 μL of MEM. Mix the solution by vortexing. e) Incubate for 30 minutes. 3. Lipofectamine-50 Control Preparation (Based on Manufacturer's Instructions) a) Place 13.5 μL of 0.04 μg / μL mRNA solution in a 1.5 mL sterile Eppendorf tube. b) Add 527 μL of MEM. c) Add 2.16 μL of Lipofectamine stock solution. Vortex. d) Incubate for 15 minutes. 4. Lipofectamine-6 control preparation: a) Place 45 μL of Lipofectamine-50 solution into a 1.5 mL sterile Eppendorf tube. b) Add 315 μL of MEM. Vortex. c) Incubate for 15 minutes.

[0332] Measurement of size and size distribution by dynamic light scattering (Method B) 1. Transfer 100 uL of freshly prepared LNP formulation into a DLS microcuvette. 2. Place the formulation into a Zetasizer that has been preheated to 37°C. 3. Allow the sample to equilibrate for 5 minutes. 4. Take size measurements in triplicate (settings: auto-adjust position and gain). 5. For QC, examine the correlation curve for disturbances. Report the Z-average and PDI based on the cumulant fit.

[0333] Encapsulation efficiency (Method B) Required solution: Ribogreen (Invitrogen / Thermofisher, catalog number 10207502) [Table 4] 0.33ug / uL mRNA solution (RiboPro, commercially available mRNA, eGFP with Cap1) in DEPC-treated water 1X TE (Tris-EDTA) buffer solution (10 mM Tris-HCl, 1 mM EDTA, pH 7.5) 0.1% Triton X-100 in 1X TE (Tris-EDTA) buffer solution

[0334] procedure: 1. Prepare RiboGreen working solution: a) Dilute RiboGreen reagent in 1X TE buffer according to manufacturer's instructions (1:200 dilution). 2. Prepare RNA standards: a) Dilute RNA standards of known concentrations in 1X TE buffer to create a series of standards with different RNA concentrations ranging from 0.1 to 1,000 ng / mL. b) Aliquot 100 μL of each standard into separate wells of a black 96-well plate. 3. Prepare liposome samples: a) Place 2.9 uL of 0.33 ug / uL mRNA solution into an Eppendorf tube. b) Add 1.94 µL of the ethanol solution of the lipid formulation and mix immediately by pipetting up and down several times (NB! Before transferring, move the solution up and down several times to saturate the pipette tip with ethanol vapor). c) Incubate for 15 minutes. d) Add 268 uL of 1x TE buffer. Mix the solution by vortexing. e) Incubate for 30 minutes. Transfer 100uL of the resulting sample to another Eppendorf and dilute with an additional 100uL of 1x TE buffer. Vortex briefly = control sample g) Transfer 100uL of the resulting sample to another Eppendorf and dilute with 100uL of 0.1% Triton X-100 solution. Vortex briefly and incubate at 37°C for 15 minutes = dissolved sample. h) Aliquot 100 μL of the control and lysis samples into separate wells of a black 96-well plate. 4. Perform RiboGreen assay: a) Add 100 μL of RiboGreen working solution to each well containing RNA standards and liposome samples. b) Gently mix the contents of the wells by pipetting up and down or by shaking the plate on an orbital shaker. c) Incubate the plate in the dark at room temperature for 5-10 minutes. d) Using a fluorescence microplate reader, measure the fluorescence intensity of each well at an excitation wavelength of 480 nm and an emission wavelength of 525 nm. e) Record the fluorescence values of the RNA standards and liposome samples. 5. Calculate mRNA encapsulation efficiency: a) Plot an RNA standard curve by plotting RNA concentration (ng / mL) on the x-axis and the corresponding fluorescence intensity on the y-axis. Fit the data to a linear regression model. b) Determine the mRNA concentration in the liposome samples by interpolating the fluorescence values onto the standard curve. c) Calculate the mRNA encapsulation efficiency as a percentage of the amount of mRNA in the liposome control sample versus the liposome lysed sample.

[0335] Transfection efficiency with GFP-mRNA (Method B) Required solution: MEM (Sigma, Catalog No. M5650-500mL) Fetal bovine serum, FBS (Sigma, Cat. No. F7524-500mL) Solution of formulation (see above) Diluent: 10 mL of MEM + 0.036 mL of ethanol

[0336] Phosphate buffered saline, PBS procedure: 1. Fill the edge wells of a 96-well plate with 100 μL medium. 2. Plate 10,000 HeLa cells per well in a 96-well plate. Do not use the edge wells. A total of 60 wells should be seeded. Incubate for 24 hours at 37°C in MEM + 10% FBS in a humidified atmosphere with 5% CO2. 3. Examine under a microscope. Confluency should be at or near 80%. 4. Gently remove (aspirate) the medium. Add 50 μL of the following formulation: a) 6 wells with diluent - negative control b) 6 wells with Lipofectamine-50 - positive control c) 6 wells with Lipofectamine-6 - secondary positive control d) 6 wells per formulation - test samples. 5. Incubate the plate at 37°C for 1 hour. 6. Add 50 μL of MEM + 20% FBS (diluted to 10%). 7. Place the plates in an incubator at 37° C. in a humidified atmosphere with 5% CO 2 for 23 hours (total incubation of 24 hours). After 24 hours, aspirate the medium without disturbing the cells. Gently wash the cells with 100 μL of warm PBS. Aspirate the PBS. 9. Add 100 μL of fresh PBS to the washed cells and read GFP fluorescence on a plate reader. 10. This can be followed by assessment of viability by MTT assay.

[0337] Assessment of cell viability by MTT assay (Method B) Required solution: MEM (Sigma, Catalog No. M5650-500mL) Fetal bovine serum, FBS (Sigma, Cat. No. F7524-500mL) Thiazolyl blue tetrazolium bromide, MTT (TCI Chemicals, catalog number D0801-5G) Formulation solution (see "Preparation of GFP mRNA-loaded LNP" protocol) Diluent: 10 mL of MEM + 0.036 mL of ethanol

[0338] Phosphate buffered saline, PBS procedure: 1. Plate 10,000 HeLa cells per well in a 96-well plate. Do not use the edge wells. A total of 60 wells should be seeded. Incubate for 24 hours at 37°C in MEM + 10% FBS in a humidified atmosphere with 5% CO2. 2. Examine under a microscope. Confluency should be at or near 80%. 3. Gently remove (aspirate) the medium. Add 50 μL of the following formulation: a) 6 wells with diluent - negative control b) 6 wells with Lipofectamine-50 - positive control c) 6 wells with Lipofectamine-6 - secondary positive control d) 6 wells per formulation - test samples. 4. Incubate the plate at 37°C for 1 hour. 5. Add 50 μL of MEM + 20% FBS (diluted to 10%). 6. Place plates in incubator at 37°C for 23 hours (total incubation of 24 hours). 7. Prepare a 1 mg / mL MTT solution in sterile PBS. Filter sterilize the solution using a 0.22 μm filter and protect from light. This solution needs to be prepared fresh prior to the assay. 8. After the treatment period, carefully remove the treatment medium from each well. a. Add 100 μL of diluted MTT solution to each well. b. Incubate the plate for 2-4 h at 37 °C in a humidified atmosphere with 5% CO2. 9. After incubation, carefully remove the MTT solution from each well without disturbing the formazan crystals. Add 100-150 μL of solubilization solution (0.04 M HCl in isopropanol) to each well to dissolve the formazan crystals. To ensure complete solubilization, gently pipette up and down or shake the plate on an orbital shaker for 5-10 minutes. 10. Using a microplate reader, measure the absorbance of each well at 570 nm. Measure the absorbance at a reference wavelength of 650 nm and subtract the background absorbance. 11. Calculate relative cell viability (%) by comparing with the blank (untreated culture).

[0339] The results of the above experiments using lipids according to the invention and reference compounds are summarized in Table 5 below. [Table 5-1] [Table 5-2] [Table 5-3]

[0340] conclusion Thanks to the innovative modular approach leading to novel ionizable cationic lipid libraries as described in this invention, a broad landscape of compound space becomes readily accessible. By utilizing commercially available starting materials and introducing a proprietary borane catalyst (described in WO 2022 / 129966), compounds of formula (I) can be synthesized.

[0341] Findings from LNP formulation and transfection studies provide evidence that the novel silicon-incorporated lipids described in this invention result in nanoparticles with appropriate size, polydispersity index (PDI), and zeta potential. Furthermore, the apparent pKa values consistent with the optimal range were determined in certain instances.

[0342] Furthermore, lipid nanoparticles formed from lipids of formula (I) demonstrated the ability to deliver GFP and luciferase mRNA into cells while exhibiting low to moderate cytotoxicity. Notably, a significant number of lipids of formula (I) from this study exhibited comparable or even superior transfection efficacy when compared to the reference compound ALC-0315.

Claims

1. Compounds having the structure of formula (I) 【Chemistry 1】 or its salt or stereoisomer [In the formula: G １ is unsubstituted C ２ ~C ９ Alkilen, - (CH ２ ) ｘ -CH=CH-(CH ２ ) ｙ - (wherein x is an integer selected from 1 to 6, y is an integer selected from 1 to 6, and the sum of x + y is an integer selected from 2 to 7), or -(CH ２ ) ｗ -X-(CH ２ ) ｚ -(wherein, w is an integer selected from 1 to 7, z is an integer selected from 2 to 7, the sum of w + z is an integer selected from 3 to 8, and in the formula, -(CH ２ ) ｚ - is bonded to N, and X is selected from O, S, SO and SO ２ ) T １ teeth, 【Chemistry 2】 And in the formula, b １ G １ It is a combination with, X １ and X ２ They are either the same or different, and each independently represents O or S. R １ In both cases, one S, SO, SO can be selected at will. ２ , O, or Si(R ａ ) ２ (In the formula, R ａ C １ ~C ６ A linear C(C) containing an alkyl group at any position within the carbon chain, provided that the heteroatom is not located at the alpha or omega position of the carbon chain. １ ~C １７ Alkyl, non-linear C ３ ~C １７ Alkyl, contains one double bond, however, the double bond and X ２ at least one -CH between ２ - C is a condition that there is a base. ３ ~C １７ Alkenyl, or the first double bond and X ２ at least one -CH between ２ - Polyunsaturated C, provided it has a group ８ ~C ２０ It is Alkenil, or R １ teeth, 【Transformation 3】 And in the formula, R １７ , R １８ and R １９ These are either the same or different, and each is independently H, OH, and -C. １ ~C ６ It may be an alkoxy or fluorine, R ２ teeth, In either case, one S, SO, SO is chosen at will. ２ , O, or Si(R ｂ ) ２ (In the formula, R ｂ C １ ~C ６ A linear C(C) containing an alkyl group at any position within the carbon chain, provided that the heteroatom is not located at the alpha or omega position of the carbon chain. １ ~C １７ Alkyl, non-linear C ３ ~C １７ Alkyl, contains one double bond, however, the double bond and X １ and X ２ Between the carbons linking the two is at least one -CH ２ - C is a condition that there is a base. ３ ~C １７ Alkenyl, or the first double bond and X １ and X ２ Between the carbons linking the two is at least one -CH ２ - Polyunsaturated C, provided it has a group ８ ~C ２０ It is Alkenil, or R ２ teeth, 【Chemistry 4】 And in the formula, R ２０ , R ２１ and R ２２ These are either the same or different, and each is independently H, OH, and -C. １ ~C ６ It may be an alkoxy or fluorine, However, R １ and R ２ Both simultaneously, 【Transformation 5】 and 【Transformation 6】 It is conditional on the fact that it cannot be, or R １ R is formed via alkylene or monounsaturated alkenyl. ３ Connected to C ５ ~C ３０ Forming a member ring, or R ２ R is formed via alkylene or monounsaturated alkenyl. ３ Connected to C ５ ~C ３０ A member ring is formed, where X １ and X ２ The carbon atoms bonded to the carbon atoms that connect them are numbered, and the first or second R ２ The carbon atoms may be optionally replaced by O or S heteroatoms, or R ２ is connected to R via an alkylene or monovalent unsaturated alkenyl to form a C １ -C ５ to C ３０ member ring, where the carbon atom bonded to the carbon connecting X １ and X ２ and numbered the first or second from the carbon atom bonded to the carbon connecting X ２ carbon atom of R may optionally be replaced by an O or S heteroatom, R ３ teeth, 【Transformation 7】 And, R ５ -b １ teeth, 【Transformation 8】 And, During the ceremony, b ２ is, X １ It is a coupling to, Y １ is -O- or -CH ２ - or -O-CH ２ -CH ２ -, where -CH ２ - is bonded to Si, Each X ３ Independently, C １ ~C ４ Alkyl or C １ ~C ４ Selected from the group consisting of alkoxys, R ４ In both cases, one S, SO, SO can be selected at will. ２ , O, or Si(R ｃ ) ２ (In the formula, R ｃ C １ ~C ６ A linear C(C) containing an alkyl group at any position within the carbon chain, provided that the heteroatom is not located at the alpha or omega position of the carbon chain. ２ ~C １７ Alkyl or non-linear carbon ３ ~C １７ Alkyl, contains one double bond, however, the double bond and Y １ at least one -CH between ２ - C is a condition that there is a base. ３ ~C ２０ Alkenyl, or the first double bond and Y １ at least one -CH between ２ - Polyunsaturated C, provided it has a group ８ ~C ２０ It is Alkenil, or R ４ teeth, 【Chemistry 9】 And in the formula, b ３ is Y １ It is a combination with, R ６ , R ７ , R ８ These are either the same or different, and each is independently H, OH, and -C. １ ~C ６ It may be an alkoxy or fluorine, D １ teeth, 【Chemistry 10】 Selected from the group consisting of, in the formula, b ４ This is a bond with nitrogen, R ９ C １ ~C ６ Alkyl, cyclopentyl, cyclohexyl, hydroxyl, hydroxymethyl, hydroxyethyl, phenyl, benzyl, 4-hydroxybenzyl, 【Chemistry 11】 Even if that is the case, R １０ and R １１ H and C are independent of each other. １ ~C ６ Selected from alkyl groups, m is an integer selected from 1 to 6. n is an integer selected from 0 to 6. o is an integer selected from 0 to 6. p is an integer selected from 2 to 6. q is an integer selected from 0 to 6. j is an integer selected from 1 to 4. Cy １ C is a carbon atom that is optionally substituted with one or more -OH groups. ３ ~C ６ It is cycloalkyl, or Cy １ This is a pyranose or furanose ring that can be linked via any of its OH groups, wherein the pyranose or furanose ring can optionally be -NH-CO-CH ３ It is substituted with a group, adenine, guanine, uracil, cytosine, thymine, monosaccharide or oligosaccharide, or a 4, 5, 6 or 7-membered heterocycle containing 1, 2, 3 or 4 heteroatoms selected from N, O or S, or Cy １ is a 4, 5, 6, or 7-membered heterocycle containing 1, 2, 3, or 4 heteroatoms selected from O, N, or S, where the heterocycle is optionally R １２ It is replaced by Here, R １２ C １ ~C ６ This represents a pyranose or furanose ring bonded to a 4, 5, 6, or 7-membered heterocyclic ring by an alkyl group, an arginine-containing peptide, or the ring carbon atom thereof, wherein the pyranose or furanose ring is -NH-CO-CH ３ The group is optionally substituted with adenine, guanine, uracil, cytosine, thymine, or a monosaccharide or oligosaccharide. R １２ b may be a group selected from (d), (e), or (f), where b ４ This is a bond with a heterocycle, and is m, n, o, p, R ９ , R １０ and R １１ This is as defined above. Or R １２ teeth, 【Chemistry 12】 It may also be a base, where r is an integer selected from 1 to 4, and Cy ２ C １ ~C ６ A 4, 5, 6, or 7-membered heterocycle containing 1, 2, 3, or 4 heteroatoms selected from O, N, and S, which are optionally substituted with alkyl groups. P is, (i)G ２ -T ２ {During the ceremony, G ２ The above G １ It is defined as, here, G １ and G ２ They may be the same or different. T ２ The above T １ It is defined as, b １ is G ２ It is a combination with T １ and T ２ They may be the same or different, or ())) ２  ３ {During the ceremony, G ２ As stipulated above, T ３ teeth, 【Chemistry 13】 And in the formula, b ５ G ２ It is a combination with, X ４ and X ５ They may be the same or different, and each can be independently O, S, or NR ｄ And here, R ｄ H, C １ ~C ６ Alkyl, -OH, or C １ ~C ６ It is an alkoxy, R １３ Both can be arbitrarily selected as S, SO, SO ２ , O, Si(R ｅ ) ２ (In the formula, R ｅ C １ ~C ６ A linear carbon atom containing one of the alkyl groups at any position in the carbon chain, provided that the heteroatom is not at the alpha or omega position of the carbon chain. ２ ~C １７ Alkyl, non-linear C ３ ~C １７ Alkyl, contains one double bond, however, the double bond and X ５ at least one -CH between ２ - C is a condition that there is a base. ３ ~C ２０ Alkenyl, or the first double bond and X ５ at least one -CH between ２ Polyunsaturated C, provided that - is present. ８ ~C ２０ Is it alkenil, or R １３ teeth, 【Chemistry 14】 And in the formula, R ２３ , R ２４ , R ２５ They are either the same or different, and each is independently H, OH, and -C. １ ~C ６ It may be an alkoxy or fluorine, R １４ Both can be arbitrarily selected as S, SO, SO ２ , O, Si(R ｆ ) ２ (In the formula, R ｆ C １ ~C ６ A linear carbon atom containing one of the alkyl groups at any position in the carbon chain, provided that the heteroatom is not at the alpha or omega position of the carbon chain. ２ ~C １７ Alkyl, non-linear C ３ ~C １７ Alkyl, contains one double bond, however, the double bond and X ４ and X ５ Between the carbons linking the two is at least one -CH ２ - C is a condition that there is a base. ３ ~C ２０ Alkenyl, or the first double bond and X ４ and X ５ Between the carbons linking the two is at least one -CH ２ Polyunsaturated C, provided that - is present. ８ ~C ２０ Is it alkenil, or R １４ teeth, 【Chemistry 15】 And in the formula, R ２６ , R ２７ , R ２８ They are either the same or different, and each is independently H, OH, and -C. １ ~C ６ } May be alkoxy or fluorine} port(iii)T ４ {During the ceremony, T ４ teeth, 【Chemistry 16】 And in the formula, b ６ This is a bond with a nitrogen atom, R ２９ , R ３０ , R ３１ These may be the same or different, and each can be independently H, OH, and -C. １ ~C ６ Alkoxy or fluorine, It contains one double bond, but there is at least one -CH between the double bond and N. ２ C is a condition that - exists ４ ~C ２０ Alkenil, or Between the first double bond and N there is at least one -CH ２ Polyunsaturated C, provided that - is present. ８ ~C ２０ [May be selected from Alkenil]

2. G １ and G ２ (If present) they are the same or different, and each independently, linear C ４ ~C ９ Alkylene, preferably C ５ ~C ９ They are alkylenes, or each independently, linear C ５ , C ６ , C ７ , or C ９ The compound according to claim 1, wherein it is an alkylene.

3. R １ is linear C １ , C ２ , C ４ , C ６ , C ７ , C ８ , C ９ , C １０ , or C １２ Alkyl or R １ is linear C ９ It is an alkenil and / or R ２ is linear C １ , C ３ , C ５ , C ６ , C ７ , C ８ , C ９ , or C １１ It is alkyl, preferably R １ is linear C ２ , C ８ , C １０ Alkyl or R １ is linear C ９ It is an alkenil and / or R ２ is linear C １ , C ３ , C ７ , or C ９ The compound according to claim 1, wherein it is alkyl.

4. T １ (c) and R １ is linear C ２ , C ４ , C ６ , C ７ , C ８ , C ９ , C １０ , or C １２ Alkyl or R １ is linear C ９ It is an alkenyl, R ２ is linear C １ , C ３ , C ５ , C ６ , C ７ , C ８ , C ９ , or C １１ It is alkyl, preferably R １ is linear C ２ , C ８ , C １０ Alkyl or R １ is linear C ９ It is an alkenyl, R ２ is linear C １ , C ３ , C ７ , or C ９ The compound according to claim 3, wherein it is alkyl.

5. P is G ２ -T ２ The compound according to claim 1.

6. The compound according to claim 3, wherein P is G2-T2.

7. G １ -T １ and G ２ -T ２ The compound according to claim 5, wherein the two are identical.

8. P is G ２ -T ３ The compound according to claim 1.

9. The compound according to claim 3, wherein P is G2-T3.

10. T １ -G １ However, the following structure 【Chemistry 17】 The compound according to claim 8, having one of the following.

11. T ３ However, the following structure [Chemistry 18] (In the formula, b ５ G ２ The compound according to claim 8, having a bond with (a bond with).

12. T3 has the following structure 【Chemistry 19】 The compound according to claim 10, having (wherein b 5 is a bond with G 2).

13. T ３ However, the following structure 【Chemistry 20】 (In the formula, b ５ G ２ The compound according to claim 8, having one of the following (a bond with).

14. T3 has the following structure 【Chemistry 21】 The compound according to claim 10, having one of the following (wherein b 5 is a bond with G 2).

15. T ３ However, the following structure 【Chemistry 22】 (In the formula, b ５ G ２ The compound according to claim 8, having one of the following (a bond with).

16. T3 has the following structure 【Chemistry 23】 The compound according to claim 10, having one of the following (wherein b 5 is a bond with G 2).

17. T ３ However, the following structure 【Chemistry 24】 (In the formula, b ５ G ２ The compound according to claim 8, having a bond with (a bond with).

18. T3 has the following structure 【Chemistry 25】 The compound according to claim 10, having (wherein b 5 is a bond with G 2).

19. P is T ４ The compound according to claim 1.

20. T ４ but, 【Chemistry 26】 (In the formula, b ６ This is a bond with a nitrogen atom, R ２９ , R ３０ , R ３１ These may be the same or different, and each can be independently H, OH, and -C. １ ~C ６ (May be alkoxy or fluorine), or Between the first double bond and N there is at least one -CH ２ Polyunsaturated C, provided that - is present. ８ ~C ２０ The compound according to claim 19, which is an alkenyl.

21. T １ -G 1 has the following structure 【Chemistry 27】 The compound according to claim 20, having one of the following.

22. T ４ However, the following structure 【Chemistry 28】 (In the formula, b ６ The compound according to claim 20, wherein the bond is with a nitrogen atom.

23. T4 has the following structure 【Chemistry 29】 The compound according to claim 21, having (wherein b 6 is a bond with a nitrogen atom).

24. D １ However, the structure is as follows: 【Transformation 30】 A compound according to any one of claims 1 to 23, having one of the following.

25. D １ However, the structure is as follows: 【Chemistry 31】 (In the formula, q is an integer selected from 1 to 4, and b ４ A compound according to any one of claims 1 to 23, having one of the following (where is a bond with nitrogen).

26. D １ However, the structure is as follows: 【Chemistry 32】 A compound according to claims 1 to 23, having one of the following.

27. The compound according to claim 1 having any of the following structures: Table 1-1 Table 1-2 Table 1-3 Table 1-4 Table 1-5 Table 1-6 Table 1-7 Table 1-8 Table 1-9 Table 1-10 Table 1-11 Table 1-12 Table 1-13 Table 1-14 Table 1-15 Table 1-16

28. Compounds having any of the following structures (Ia), (Ib), or (Ic) 【Transformation 33】 (In the formula, D １ G １ , T １ And P is as defined in claim 1, Z １ teeth, 【Transformation 34】 And in the formula, b ４ This is a bond with N, s is an integer from 1 to 6. t is an integer between 2 and 6.

29. Compounds having the following structure (II) 【Chemistry 35】 (In the formula, G １ This is as defined in claim 1, T １ teeth, 【Transformation 36】 And in the formula, b １ , X １ and X ２ , R １ , R ２ , R ３ and R ５ This is as described in claim 1, X ６ (This is selected from Cl, Br, I, OMs, OTs, OTf).

30. The compound according to claim 29, having any of the following structures: Table 2-1 Table 2-2 Table 2-3 Table 2-4

31. A therapeutic agent and lipid nanoparticles comprising the compound described in claim 1.

32. A therapeutic agent and lipid nanoparticles comprising the compound described in Claim 10.

33. A therapeutic agent and lipid nanoparticles comprising the compound described in Claim 11.

34. A therapeutic agent and lipid nanoparticles comprising the compound described in Claim 13.

35. A therapeutic agent and lipid nanoparticles comprising the compound described in Claim 15.

36. A therapeutic agent and lipid nanoparticles comprising the compound described in Claim 17.

37. A therapeutic agent and lipid nanoparticles comprising the compound described in Claim 27.

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