New tags for liquid phase peptide synthesis

Abstract

The invention relates to a compound of formula (I) wherein X is selected from the group consisting of-O-(CH2) n-wherein n is 0 to 4, R1 and R2 are independently selected from the group consisting of C11-C25 alkyl groups, SP is a spacer, in particular selected from the group consisting of saturated C4-C8 alkyl groups, unsaturated C4-C8 alkyl groups and substituted or unsubstituted C6 aromatic compounds, in particular substituted C6 aromatic compounds are alkyl substituted C6 aromatic compounds, Y is a heteroatom, n is 0 to 4, and R1 and R2 are independently selected from the group consisting of C11-C25 alkyl groups, SP is a spacer, in particular selected from the group consisting of saturated C4-C8 alkyl groups, unsaturated C4-C8 alkyl groups, and substituted or unsubstituted C6 aromatic compounds, in particular substituted C6 aromatic compounds are alkyl substituted C6 aromatic compounds. L is a peptide synthesis linker, in particular selected from the group consisting of-O-and-NH-, L is a peptide synthesis linker, and m is 0 or 1, in particular m is 1.

Description

Technical Field

[0001] This invention relates to novel tags for liquid-phase peptide synthesis. Background Technology

[0002] In 1963, Merrifield invented solid-phase peptide synthesis (SPPS), revolutionizing peptide chemistry by using resins that allowed coupling and deprotection reactions to proceed in a heterogeneous system, thus removing excess reagents and byproducts through a simple washing step (Merrifield, RB, J. Am. Chem. Soc. 1963, 85(14), 2149–2154). Although efficient SPPS requires excess reagents and large amounts of solvent, the commonly used Fmoc-tBu strategy can be easily scaled up and automated for large-scale peptide production. However, in the context of green chemistry, the large amounts of waste and harmful solvents used in SPPS, such as DMF, NMP, and DCM, must be addressed. In contrast, liquid-phase peptide synthesis (LPPS) represents a method suited to these requirements, as the reaction is carried out in solution using soluble tags attached to the growing peptide chain (see review: Albericio, F. et al. Chem. Rev. 2022, 16, 13516–13546). LPPS can be performed with less solvent and excess reagent, and also offers the possibility of using green solvents such as tetrahydrofuran (Chiba, K. Tamaki, H. et. al. Org. Process Res. Dev. 2019, 23, 11, 2576–2581) and cyclopentyl methyl ether (Kubota, H. et. al. Molecules 2021, 26(12), 3497). Starting with the early PEG-based methods of Mutter and Bayer (Bayer, E. and Mutter, M., Nature 1972, 237, 512–513; Mutter, M. and Bayer, E., Angew. Chem., Int. Ed. Engl. 1974, 13, 88–89), Tamaki et al. (Tamaki, H. et. al. Bull. Chem. Soc. Jpn. 2001, 74, 733–738) invented substituted hydrophobic benzyl alcohols (HABs) for tag-assisted LPPS, which have been improved by different groups (e.g., Sunazuka, T. et. al. Tetrahedron 2011, 67, 6633–6643 and Takahashi, D. et. al. Angew. Chem., Int. Ed. 2017, 56, 7803–7807). These works successfully used soluble HAB tags to synthesize small to medium-sized peptides using the Fmoc method, while typically purifying the desired peptides by precipitation or membrane-assisted filtration and, in some cases, by water treatment procedures.

[0003] Based on the aforementioned prior art, the object of the present invention is to provide means and methods for synthesizing novel tags for peptides in solution. This object is achieved through the subject matter of the independent claims of this specification and the further advantageous embodiments described in the dependent claims, examples, drawings, and general description. Summary of the Invention

[0004] The first aspect of the present invention relates to compounds of formula (I).

[0005]

[0006] in,

[0007] X selects freely –O –(CH2) n – A group consisting of n, where n is between 0 and 4.

[0008] R 1 and R 2 Independent choice of C 11 –C 25 The group consisting of alkyl groups,

[0009] SPs are spacers, particularly selected from the group consisting of saturated C4–C8 alkyl, unsaturated C4–C8 alkyl, and substituted or unsubstituted C6 aromatic compounds, especially substituted C6 aromatic compounds that are alkyl-substituted C6 aromatic compounds.

[0010] Y is a heteroatom, specifically chosen from the group consisting of –O– and –NH–.

[0011] L is the peptide synthesis linker, and

[0012] m can be 0 or 1, especially m can be 1.

[0013] Terms and Definitions

[0014] For the purpose of interpreting this specification, the following definitions will apply, and where appropriate, terms used in the singular will also include the plural, and vice versa. In the event of any conflict between any definition set forth below and any reference incorporated herein by reference, the definition set forth herein shall prevail.

[0015] As used herein, the terms “comprising,” “having,” “containing,” and “including,” as well as other similar forms and their grammatical equivalents, are intended to be equivalent in meaning and are open-ended, because one or more items following any of these terms do not imply an exhaustive list of those items or that the list is limited to only the listed items. For example, an article “comprising” components A, B, and C may consist of components A, B, and C (i.e., contain only C), or may contain not only components A, B, and C, but may also include one or more other components. Therefore, it is intended and understood that “comprising” and its similar forms and their grammatical equivalents include disclosures of embodiments “consistently consisting of” or “composed of.”

[0016] Where numerical ranges are provided, it should be understood that, unless the context explicitly specifies otherwise, every intermediate value of one-tenth of the unit of the lower limit between the upper and lower limits of the range, and any other stated value or intermediate value within the range, is covered by the invention but is subject to any specific exclusions within the range. Where the range includes one or two limits, the range excluding any one or both of those included limits is also included in this disclosure.

[0017] The “about” values ​​or parameters mentioned in this article include (and describe) variations relating to that value or parameter itself. For example, a description of “about X” includes a description of “X”.

[0018] As used herein, including in the appended claims, the singular forms “a,” “or,” and “the” include plural references unless the context clearly indicates otherwise.

[0019] "And / or" is used here as a specific description of each of two particular features or components, with or without other features or components. Therefore, the term "and / or" as used in phrases such as "A and / or B" is intended to include "A and B", "A or B", "A" (alone), and "B" (alone). Similarly, the term "and / or" as used in phrases such as "A, B, and / or C" is intended to cover each of the following: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone).

[0020] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art (e.g., in cell culture, molecular genetics, nucleic acid chemistry, hybridization techniques and biochemistry, organic synthesis). Standard techniques are used for molecular, genetic, and biochemical methods (see generally Sambrook et al., Molecular Cloning: A Laboratory Manual, 4th ed. (2012) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY and Ausubel et al., Short Protocols in Molecular Biology (2002) 5th Ed., John Wiley & Sons, Inc.) as well as chemical methods.

[0021] In the context of this specification, the term adapter refers to a molecule used in Fmoc solid-phase peptide synthesis (SPPS) that is attached to a resin on which SPPS is performed and to the peptide formed. The adapter can be separated from the peptide by a spacer. Once the desired peptide length is reached, the adapter is cleaved off the peptide.

[0022] In the context of this specification, the term spacer refers to a flexible hydrophobic compound consisting of hydrocarbon atoms that connect the connector molecule and the tag core.

[0023] In the context of this specification, the term "tag" refers to a molecule on which a peptide sequence is formed. Tags are typically attached to the N-terminus or C-terminus of the formed peptide.

[0024] The formulas in this specification follow organic chemistry conventions and do not show hydrogen atoms on the carbon skeleton. Carbon is tetravalent, and unless otherwise indicated, bonds not shown are assumed to be hydrogen. Hydrogen can be exchanged with deuterium without altering the bulk chemical properties of the molecule; however, in the case of dye or pharmaceutical molecules, the exchange of hydrogen with deuterium may result in changes in the spectral properties of the molecule or its acceptor interactions. Unless otherwise expressly stated herein, the disclosure of formulas explicitly or implicitly shown by convention restated in the first sentence of this paragraph covers molecules in which one or more hydrogen atoms are exchanged with deuterium.

[0025] In the context of this specification, the term saturated alkyl refers to saturated straight-chain or branched hydrocarbons.

[0026] In the context of this specification, the term unsaturated alkyl refers to straight-chain or branched hydrocarbons in which one or more carbon-carbon bonds may be unsaturated.

[0027] In the context of this specification, the term alkyl refers to a saturated straight-chain, branched, or cyclic hydrocarbon consisting of a specified number of carbon atoms. Examples of alkyl residues include, but are not limited to, n-butyl, isobutyl, n-pentyl, 2-methylbutyl, 3-methylbutyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, cyclopentyl, cyclohexyl, methylcyclopentyl, methylcyclohexyl, heptyl, decyl, and dodecyl. In some embodiments, the C5 alkyl group is a pentyl or cyclopentyl moiety, the C6 alkyl group is a hexyl or cyclohexyl moiety, and the C7 alkyl group is a heptyl or cyclohepyl; this also applies to higher alkyl groups as commonly understood by those skilled in the art.

[0028] In the context of this specification, the term alkyl-substituted C6 aryl refers to cycloaromatic C6 hydrocarbons. The C6 aryl group may be further substituted in one or more carbon atoms with a group selected from saturated or unsaturated hydrocarbons (broadly defined as alkyl). Examples include, but are not limited to, phenyl, benzyl, xylene, and tolyl. Detailed Implementation

[0029] The first aspect of the present invention relates to compounds of formula (I).

[0030]

[0031] in,

[0032] X selects freely –O –(CH2) n – A group consisting of n, where n is between 0 and 4.

[0033] R 1 and R 2 Independent choice of C 11 –C 25 The group consisting of alkyl groups,

[0034] SP is a spacer, specifically selected from the group consisting of saturated C4–C8 alkyl groups, unsaturated C4–C8 alkyl groups, and substituted or unsubstituted C6 aromatic compounds, especially substituted C6 aromatic compounds which are C6 aromatic compounds.

[0035] Y is a heteroatom, specifically chosen from the group consisting of –O– and –NH–.

[0036] L is the peptide synthesis linker, and

[0037] m can be 0 or 1, especially m can be 1.

[0038] The compound is used as a tag for peptide extension in a greener solvent compared to SPPS. Furthermore, the novel tag allows for simple post-processing of the coupling reaction via simple phase separation. The resulting tag-conjugated peptide remains in the organic phase and can be used directly for the next coupling step without any further purification. The synthesis of the desired tag is based on readily available and inexpensive starting materials, providing an affordable molecule for LPPS.

[0039] In some implementations, n is 0 or 1.

[0040] In some implementations, n is 0.

[0041] In some implementations, R 1 and R 2 They are independent of each other as branches or replace C. 11 –C 25 alkyl.

[0042] In some implementations, R 1 and R 2 Independent choice of C 13 –C 25 A group composed of alkyl groups.

[0043] In some implementations, R 1 Choose C freely 17 –C 25 A group composed of alkyl groups.

[0044] In some implementations, R 1 Choose C freely 21 –C 25 A group composed of alkyl groups.

[0045] In some implementations, R 2 Choose C freely 17 –C 25 A group composed of alkyl groups.

[0046] In some implementations, R 2 Choose C freely 21 –C 25 A group composed of alkyl groups.

[0047] In some implementations, R 1 and R 2 For branching or replacing C 11 –C 25 alkyl.

[0048] In some implementations, R 1 and R 2 Choose C freely 13 –C 25 A group composed of alkyl groups.

[0049] In some implementations, R 1 and R 2 Choose C freely 17 –C 25 A group composed of alkyl groups.

[0050] In some implementations, R 1 and R 2 Choose C freely 21 –C 25 A group composed of alkyl groups.

[0051] In some implementations, Y1 is –NH– and Y2 is –NH– or –O–.

[0052] In some implementations, Y1 is –NH– and Y2 is –NH–.

[0053] In some embodiments, SP is selected from the group consisting of saturated C4–C8 alkyl, unsaturated C4–C8 alkyl, and substituted C6 aromatic compounds.

[0054] In some embodiments, SP is selected from the group consisting of saturated C4–C8 alkyl and alkyl-substituted C6 aromatic compounds.

[0055] In some embodiments, SP is selected from the group consisting of saturated C4–C8 alkyl groups.

[0056] In some embodiments, SP is selected from the group consisting of saturated C5–C7 alkyl and alkyl-substituted C6 aromatic compounds.

[0057] In some embodiments, SP is selected from the group consisting of saturated C5–C7 alkyl groups.

[0058] In some embodiments, the connector L is selected from the group consisting of Rink, Sieber, triphenylmethyl, Ramage, Wang, Sasrin, HMPB, 2-chlorotriphenylmethyl, MBHA, PAL, HMBA, and HMPA.

[0059] In some embodiments, the connector L is selected from the group consisting of Ramage, Rink, HMPA, PAL, and HMBA. In some embodiments, the connector L is selected from the group consisting of Rink, Sieber, triphenylmethyl, Ramage, Wang, Sasrin, HMPB, 2-chlorotriphenylmethyl, and MBHA. In some embodiments, the connector L is selected from the group consisting of Rink, Sieber, and triphenylmethyl.

[0060] The tag can be used for peptide synthesis in greener solvents and with less solvent compared to conventional solid-phase peptide synthesis, making this method a more environmentally friendly and cost-effective way to synthesize peptides.

[0061] Furthermore, the use of tags in peptide synthesis eliminates the need for additional purification steps, resulting in higher peptide yields compared to conventional peptide synthesis.

[0062] The invention is further illustrated by the following embodiments, from which further implementation methods and advantages can be obtained. These embodiments are for illustrative purposes only and are not intended to limit the scope of the invention.

[0063] Example

[0064] Example 1: Tag Synthesis

[0065] Preparation of 2-chloro-4,6-bis(heptadecan-9-yloxy)-1,3,5-triazine

[0066]

[0067] Under a nitrogen atmosphere, heptadecano-9-ol (48.68 g, 3.5 equivalents, 189.80 mmol) was dissolved in dry, stabilized tetrahydrofuran (500 mL), and sodium hydride (11.00 g, 60% Wt, 5.0 equivalents, 271.10 mmol) was added in portions over 10 minutes at 4 °C. After the addition was complete, the reaction was warmed to room temperature and stirred for 1 hour. Then, 2,4,6-trichloro-1,3,5-triazine (10.00 g, 1.0 equivalents, 54.23 mmol) was added in portions over 10 minutes, and the mixture was stirred at 40 °C for 40 hours.

[0068] The reaction was quenched in an ice bath with water (100 mL) for 15 min and diluted with ethyl acetate (200 mL). The pH was adjusted to pH 5 by adding 1 M HCl. The mixture was transferred to a separatory funnel and extracted. The combined organic phases were washed with brine (100 mL) and dried over MgSO4. The solvent was removed under reduced pressure to give the crude product (16.24 g, 26.0 mmol, 48.0%) as a white waxy powder.

[0069] The crude product was further purified by column chromatography (1000g, SiO2; EtOAc / n-heptane, 1:50) to obtain a pale yellow oily substance.

[0070] MS (ESI, positive ion): m / z = 624.53 [M+H] +

[0071] N 1 Preparation of 1,6-bis(heptadecane-9-yloxy)-1,3,5-triazin-2-yl)hexane-1,6-diamine

[0072]

[0073] Hexane-1,6-diamine (10.24 g, 5.0 equivalents, 88.079 mmol) was dissolved in toluene (200 mL) and stirred at room temperature for 1 hour. 2-Chloro-4,6-bis(heptadecane-9-yloxy)-1,3,5-triazine (11.00 g, 1.0 equivalents, 17.616 mmol) was dissolved in toluene (100 mL) and added to the reaction mixture. Then, diisopropylethylamine (17.00 g, 23 mL, 7.6 equivalents, 0.13 mol) was added, and the reaction was stirred at 80 °C for 48 hours. The solvent was removed under reduced pressure. The mixture was diluted with 200 mL of ethyl acetate and transferred to a separatory funnel, then extracted three times with water (100 mL) and brine (50 mL). The solvent was removed under reduced pressure to give the crude product (9.85 g, 13.98 mmol, 79.4%) as a pale yellow oil.

[0074] The product is used directly without further purification.

[0075] MS (ESI, positive ion): m / z = 704.66 [M+H] +

[0076] ((4-(2-((6-((4,6-bis(heptadecane-9-yloxy)-1,3,5-triazin-2-yl)amino)hexyl)amino)- Preparation of methyl 2-oxoylideneethoxy)phenyl)(2,4-dimethoxyphenyl)methyl)carbamate (9H-fluorene-9-yl)

[0077]

[0078] Fmoc–Rink–connector (15.33 g, 2.0 equivalent, 28.40 mmol) and HOBt (4.86 g, 2.0 equivalent, 28.40 mmol) were dissolved in dichloromethane (250 mL), and EDC HCl (5.50 g, 99% wt, 2.0 equivalent, 28.40 mmol) was added in portions over 5 minutes. After stirring at room temperature for 1 hour, the reaction was cooled in an ice bath (internal 4 °C) and 4-methylmorpholine (2.87 g, 3.2 mL, 2.0 equivalent, 28.40 mmol) was added. Then, N… 1 -(4,6-bis(heptadecane-9-yloxy)-1,3,5-triazin-2-yl)hexane-1,6-diamine (10.00 g, 1.0 equivalent, 14.20 mmol) was added in portions over 5 minutes, keeping the internal temperature below 10°C. After the addition was complete, the reaction mixture was warmed to room temperature.

[0079] After stirring at 40°C for 8 hours, the suspension was evaporated to remove dichloromethane. The crude product was diluted with ethyl acetate and washed three times with water (100 mL) and once with brine (100 mL) to give methyl ((4-(2-((6-((4,6-bis(heptadecane-9-yloxy)-1,3,5-triazin-2-yl)amino)hexyl)amino)2-oxonylethoxy)phenyl)(2,4-dimethoxyphenyl)methyl)carbamate (9H-fluorene-9-yl) ester (12.52 g, 10.21 mmol, 71.9%).

[0080] MS (ESI, positive ion): m / z = 1225.83 [M+H] +

[0081] 1 H NMR (400MHz, CD2Cl2) δ [ppm] = 7.77, 7.76 (s, 2H), 7.60–7.59 (m, 2H), 7.57–7.56 (m, 2H), 7.38–7.3 7(m,2H),7.30–7.28(m,2H),7.15–7.06(m,2H),6.86–6.78(m,2H),6.49–6.45(m,1H),6.22(s,1H) ,6.10–5.95(m,2H),5.32–5.30(m,2H),5.16(s,2H,OCH),4.42–4.38(m,2H),3.78–3.72(m,6H),3 .35–3.25(m,2H),2.78–2.76(m,2H),1.68–1.48(m,12H),1.35–1.05(m,54H),0.89–0.85(m,12H).

[0082] 13 C NMR (101MHz, CD2Cl2): δ [ppm] = 173.7, 173.4, 168.9, 168.2, 161.1, 158.6, 156 .8,156.0,144.6,141.7,136.4,134.2,129.2,127.5,125.5,121.4,120.3,11 4.8,109.8,104.8,99.6,85.8,78.4,77.4,68.0,67.9,54.1,53.8,51.2,47.8,41.2,40.5,39.1,34.5,32.3,30.0,29.9,26.9,25.8,23.1,19.3,15.8,14.3.

[0083] (2-(2-((6-((4,6-bis(heptadecane-9-yloxy)-1,3,5-triazin-2-yl)amino)hexyl)amino)- 2-Oxylideneethoxy)-10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-yl)carbamate (9H-fluorene-9-yl)methyl Preparation of esters

[0084]

[0085] Fmoc-Ramage-connector (3.95 g, 1.1 equivalent, 7.81 mmol) and HOBt (1.46 g, 1.2 equivalent, 8.52 mmol) were dissolved in DMF (40 mL), and the reaction mixture was cooled in an ice bath (internal 4 °C). 4-Methylmorpholine (1.46 g, 1.2 equivalent, 8.52 mmol) was added at 4 °C, followed by the addition of EDC HCl (2.06 g, 99% wt, 1.5 equivalent, 10.7 mmol) in two portions. Then, N... 1 5,6-bis(heptadecane-9-yloxy)-1,3,5-triazin-2-yl)hexane-1,6-diamine (5.00 g, 1.0 equivalent, 7.10 mmol) was dissolved in DMF (31 mL) and added in portions over 3 minutes, keeping the internal temperature below 10 °C. After the addition was complete, the reaction mixture was warmed to room temperature.

[0086] After stirring at 22°C for 3 hours, the crude product was diluted with 71 mL of acetonitrile and cooled to 4°C. 71 mL of water was slowly added, forming a precipitate. Another 71 mL of water was added at 22°C, and the precipitate was collected by filtration through a P3 sintered glass filter. The precipitate was washed with 70 / 30 water / acetonitrile (100 mL) and 90 / 10 water / acetonitrile (100 mL). The precipitate was then dissolved in 200 mL of 2-methyltetrahydrofuran, washed with brine (100 mL), and dried over MgSO4. The crude product was purified by MPLC (4 runs on a 24 g SiO2 column) using a DCM to DCM / EtOAc 80:20 gradient elution to give (2-(2-((6-((4,6-bis(heptadecane-9-yloxy)-1,3,5-triazin-2-yl)amino)hexyl)amino)-2-oxylideneethoxy)-10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-yl)carbamate (9H-fluorene-9-yl)methyl ester (5.39 g, 4.52 mmol, 63.7%).

[0087] MS (ESI, positive ion): m / z = 1191.87 [M+H] +

[0088] 1H NMR(400MHz,CD2Cl2)δ[ppm]=7.78(d,J=7.5Hz,2H),7.54(d,J=7.5Hz,2H),7.40(t,J=7.5Hz,2H),7.29(td,J=7.5,1.2Hz,3H),7.19(dt,J=16.7,4.9Hz,3H),6.74(d,J=2.3Hz,2H),6.52(t,J=6.0Hz,1H),5.20–5.04(m,2H),4.43(s,4H),4.20(t,J=6.5Hz,1H),3.32(dp,J=19.9,6.9Hz,6H),3.04(q,J=12.4Hz,2H),1.58(ddt,J=25.5,20.7,7.5Hz,16H),1.27(d,J=7.2Hz,54H),0.92–0.84(m,12H)。

[0089] 13 C NMR(101MHz,CD2Cl2):δ[ppm]=172.8,169.0,168.1,157.5,155.4,144.5,141.8,141.4,139.0,132.7,131.3,130.8,129.5,128.4,128.1,127.5,126.8,125.4,120.4,116.9,112.6,77.5,77.1,68.0,66.9,60.1,47.8,41.2,39.2,34.6,34.5,33.3,32.8,32.3,30.1,30.0,30.0,29.9,29.7,26.9,26.9,25.9,25.8,23.1,14.3。

[0090] Preparation of 2,4-bis((2-butyloctyl)oxy)-6-chloro-1,3,5-triazine

[0091]

[0092] Under a nitrogen atmosphere, 2-Butyloct-1-ol (2.02 g, 2.4 mL, 2.0 equivalent, 10.8 mmol) was dissolved in 2-methyltetrahydrofuran (20 mL) at room temperature. The reaction mixture was cooled to 0 °C and sodium hydride (2.17 g, 60% Wt, 10.0 equivalent, 54.20 mmol) was added in portions. After the addition was complete, the reaction mixture was refluxed for 18 hours. After cooling to -10 °C, the active alcohol was added dropwise in three portions to a cooled solution of 2,4,6-trichloro-1,3,5-triazine (1.00 g, 1.0 equivalent, 5.42 mmol) dissolved in 10 mL of 2-methyltetrahydrofuran (-10 °C). The reaction mixture was stirred and warmed to room temperature for 4 hours, then quenched with H2O, transferred to a separatory funnel, and washed with brine (50 mL). The organic phase was dried over MgSO4 to give 2,4-bis((2-butyloctyl)oxy)-6-chloro-1,3,5-triazine. The product was used directly without further purification.

[0093] MS (ESI, positive ion): m / z = 484.33 [M+H] +

[0094] N 1 Preparation of 1,6-bis((2-butyloctyl)oxy)-1,3,5-triazine-2-yl)hexane-1,6-diamine

[0095]

[0096] Hexane-1,6-diamine (6.31 g, 10.0 equivalent, 54.30 mmol) was dissolved in 2-methyltetrahydrofuran (30 mL) and stirred at elevated temperature for 10 minutes. The diamine solution was heated to 70 °C, and a solution of 2,4-bis((2-butyloctyl)oxy)-6-chloro-1,3,5-triazine (2.63 g, 1.0 equivalent, 5.43 mmol) in 2-methyltetrahydrofuran (20 mL) was added dropwise. After complete addition, the reaction mixture was stirred for approximately 1.5 hours. The reaction mixture was then cooled to room temperature and the precipitate was filtered off (G3 sintered glass). The remaining solution was diluted with ethyl acetate (600 mL). The organic layer was washed four times with water (4 × 250 mL), once with 0.5 M HCl (250 mL), and once with brine (250 mL). The combined organic phases were dried with MgSO4 and purified by column chromatography (100 g, SiO2; DCM: NH3(7N)MeOH solution 90:10) to obtain N. 1 -(4,6-bis((2-butyloctyl)oxy)-1,3,5-triazin-2-yl)hexane-1,6-diamine (1.10 g, 1.96 mmol, 2 steps 36.0%).

[0097] MS (ESI, positive ion): m / z = 564.52 [M+H] +

[0098] ((4-(2-((6-((4,6-bis((2-butyloctyl)oxy)-1,3,5-triazine-2-yl)amino)hexyl)amino Preparation of (9H-fluorene-9-yl)methyl carbamate (2,4-dimethoxyphenyl)methyl)carbamate

[0099]

[0100] Add 182 mg, 1.2 equivalents, 1.06 mmol of HOBt dihydrate to a DMF (5 mL) solution of 2-(4-((((((9H-fluoren-9-yl)methoxy)carbonyl)amino)(2,4-dimethoxyphenyl)methyl)phenoxy)acetic acid (526 mg, 1.1 equivalents, 975 μmol) and cool the mixture to 4 °C. Add 258 mg, 99% wt, 1.5 equivalents, 1.33 mmol of EDC HCl, followed by 4-methylmorpholine (359 mg, 0.39 mL, 4.0 equivalents, 3.55 mmol), and stir the mixture at 4 °C for 5 minutes. Then add N 1 A solution of 5 mL of DMF containing 4,6-bis((2-butyloctyl)oxy)-1,3,5-triazin-2-yl)hexane-1,6-diamine (526 mg, 1.1 equivalents, 975 μmol). The mixture was stirred at 4 °C for 5 minutes, then warmed and stirred at room temperature for 1 hour. The mixture was diluted with acetonitrile (10 mL) and added dropwise to 40 mL of distilled water at 4 °C. The resulting mixture was diluted with dichloromethane (150 mL) and 5 w% LiCl (50 mL) and transferred to a separatory funnel. The resulting emulsion could be clarified by adding 20 mL of ethanol. The phases were separated, and the aqueous phase was extracted twice with dichloromethane (50 mL). The combined organic phases were washed with 5 w% LiCl and brine, dried over MgSO4, and purified by MPLC (12 g SiO2 column) using a DCM to 80 / 20 DCM / EtOAc gradient to give ((4-(2-((6-((4,6-bis((2-butyloctyl)oxy)-1,3,5-triazin-2-yl)amino)hexyl)amino)-2-oxylideneethoxy)phenyl)(2,4-dimethoxyphenyl)methyl)carbamate (9H-fluorene-9-yl)methyl ester (480 mg, 442 μmol, 49.9%).

[0101] MS (ESI, positive ion): m / z = 1085.71 [M+H] +

[0102] 1H NMR(400MHz,CD2Cl2)δ[ppm]=7.78(d,J=7.6Hz,2H),7.60(s,1H),7.40(td,J=7.5,3.1Hz,2H),7.30(s,2H),7.15(d,J=8.4Hz,2H),7.09(d,J=8.2Hz,1H),6.89–6.80(m,2H),6.55(t,J=5.9Hz,1H),6.51–6.45(m,2H),5.98(d,J=8.5Hz,1H),4.43(s,4H),4.23(dd,J=8.7,5.9Hz,3H),4.15(d,J=5.8Hz,2H),3.80(s,3H),3.74(s,3H),3.38(td,J=7.1,5.9Hz,2H),3.30(q,J=6.8Hz,2H),1.60–1.47(m,4H),1.37–1.24(m,38H),0.96–0.84(m,12H)。

[0103] 13 C NMR(101MHz,CD2Cl2):δ[ppm]=172.9,168.8,168.2,161.2,158.4,156.8,144.5,141.8,136.4,129.7,128.4,128.0,127.4,125.5,125.5,120.3,114.9,104.8,99.7,70.5,70.3,68.1,55.9,55.8,47.9,41.3,39.2,38.1,32.3,31.7,31.3,30.1,30.0,29.9,29.5,27.2,26.9,26.9,23.5,23.1,14.3。

[0104] N-(3-((λ 2 -Azylyl)methyl)benzyl)-4,6-bis(heptadecyl-9-yloxy)-1,3,5-triazine-2-amine preparation

[0105]

[0106] 1,3-Phenylenediamine (7.39 g, 7.16 mL, 10.0 equivalent, 54.30 mmol) was dissolved in 2-methyltetrahydrofuran (30 mL) and stirred at elevated temperature for 10 minutes. A solution of 2-chloro-4,6-bis(heptadecane-9-yloxy)-1,3,5-triazine (3.39 g, 1.0 equivalent, 5.43 mmol) in 2-methyltetrahydrofuran (35 mL) was added dropwise. After the addition was complete, the reaction was stirred for approximately 1 hour, then cooled to room temperature and the precipitate was filtered off (G3 sintered glass). The remaining solution was diluted with ethyl acetate (600 mL). The organic layer was washed four times with water (4 × 250 mL), once with 0.5 M HCl (250 mL), and once with brine (250 mL), dried over MgSO4, and evaporated. The crude product was further purified by column chromatography (100 g, SiO2; DCM / MeOH, 95:5–91:10, followed by DCM:NH3(7N)MeOH solution 90:10) to obtain the product, which was a pale yellow oil (1.00 g, 1.39 mmol, 25.5%).

[0107] MS (ESI, positive ion): m / z = 724.67 [M+H] +

[0108] Preparation of 4-(((triisopropylsilyl)oxy)methyl)benzoic acid

[0109]

[0110] To a suspension of 4-(hydroxymethyl)benzoic acid (0.85 g, 1.0 equivalent, 5.60 mmol) in dichloromethane (30 mL), imidazole (1.10 g, 3.0 equivalent, 17.00 mmol) was added, followed by dropwise addition of triisopropylsilyl trifluoromethanesulfonate (3.50 g, 3.10 mL, 2.0 equivalent, 11.00 mmol) at 4 °C. The mixture was warmed to room temperature and then refluxed for 3 hours. Subsequently, the solvent was removed under reduced pressure, and the residue was dissolved in THF / H₂O (1:1; 30 mL). Potassium carbonate (0.77 g, 1.0 equivalent, 5.60 mmol) was then added, and the mixture was heated to ~50 °C for 1 hour. The reaction mixture was transferred to a separatory funnel and acidified to pH ~3.5 by adding 5 w% citric acid. Ethyl acetate was added, and the phases were separated. The aqueous phase was extracted with ethyl acetate, and the combined organic phases were washed twice with H₂O (2 × 30 mL) and once with brine (20 mL). The crude mixture was dried over MgSO₄ and the solvent was removed under reduced pressure. Analytical grade samples were obtained by column chromatography, but the bulk material was used directly in the next step without further purification.

[0111] 1H NMR (400MHz, CD2Cl2) δ [ppm] = 8.14–8.00 (m, 2H), 7.50 (m, 2H), 4.93 (s, 2H), 1.13–1.08 (m, 21H).

[0112] N-(3-(((4,6-bis(heptadecane-9-yloxy)-1,3,5-triazin-2-yl)amino)methyl)benzyl)-4- Preparation of (((triisopropylsilyl)oxy)methyl)benzamide

[0113]

[0114] Add 4-(((triisopropylsilyl)oxy)methyl)benzoic acid (92.5 mg, 1.2 equivalents, 300 μmol) and hydrated 1H-benzo[d][1,2,3]triazine-1- to a solution of N-(3-(aminomethyl)benzyl)-4,6-bis(heptadecano-9-yloxy)-1,3,5-triazine-2-amine (181 mg, 1.0 equivalent, 250 μmol) in dichloromethane (10 mL). Alcohol (49.8 mg, 1.3 equivalents, 325 μmol) was added, followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (71.9 mg, 1.50 equivalents, 375 μmol) and 4-methylmorpholine (0.13 g, 0.14 mL, 5.1 equivalents, 1.30 mmol). The mixture was stirred at room temperature for 2.5 hours, after which the reaction mixture was transferred to a separatory funnel and washed with 1 M KHSO4, saturated NaHCO3, and brine. The organic phase was dried over MgSO4 and the solvent was removed under reduced pressure. The crude product was further purified by MPLC (4 g SiO2 column) using a gradient elution of DCM to 80 / 20 DCM / EtOAc to give the product as a pale yellow oil (66 mg, 250 μmol, 26%).

[0115] MS (ESI, positive ion): m / z = 1014.77 [M+H] +

[0116] 1 H NMR(400MHz, CD2Cl2)δ[ppm]=8.08–8.01(m,2H),7.79–7.72(m,2H),7.47(dd,J=7.9,0.8Hz,2H),7.45–7.40(m,2H),4.92( s, 2H), 4.88 (d, J = 0.9Hz, 2H), 4.62 (dd, J = 5.9, 4.4Hz, 4H), 1.27 (d, J = 6.5Hz, 42H), 1.13–1.04 (m, 35H), 0.91–0.82 (m, 12H).

[0117] 13C NMR (101MHz, CD2Cl2): δ[ppm]=172.7,172.1,170.4,168.7,167.4,148.2,146.0,139.7,139.5,133.4,130.3,129.4,128.7,127.3,127.2 ,127.1,126.9,126.2,126.0,77.9,77.6,65.1,65.1,45.0,44.2,34.5,34.4,32.3,30.1,30.0,29.7,25.8,25.7,23.1,18.2,14.3,12.5.

[0118] Preparation of 2-chloro-4,6-bis((16-methylheptadecyl)oxy)-1,3,5-triazine

[0119]

[0120] Under a nitrogen atmosphere, 16-methyl-1-heptadecanool (2.93 g, 2.0 equivalent, 10.8 mmol) was dissolved in 2-methyltetrahydrofuran (20 mL), cooled to 0 °C, and sodium hydride (2.17 g, 60% Wt, 10.0 equivalent, 54.2 mmol) was added in portions. After the addition was complete, the reaction mixture was refluxed for 18 hours. After cooling to -10 °C, the active alcohol was added dropwise over 15 minutes to a cooled solution of 2,4,6-trichloro-1,3,5-triazine (1.00 g, 1.0 equivalent, 5.42 mmol) dissolved in 10 mL of 2-methyltetrahydrofuran (-10 °C). The reaction mixture was stirred and warmed to room temperature for 1 hour, then quenched with cold water and transferred to a separatory funnel, and washed once with saline (50 mL). The organic phase was dried with MgSO4 to give 2-chloro-4,6-bis((16-methylheptadecyl)oxy)-1,3,5-triazine.

[0121] MS (ESI, positive ion): m / z = 652.62 [M+H] +

[0122] N -(4-(λ 2 -(azoyl)butyl)-4,6-bis((16-methylheptadecyl)oxy)-1,3,5-triazine-2-amine preparation

[0123]

[0124] Butane-1,4-diamine (4.78 g, 10.0 equivalent, 54.3 mmol) was dissolved in 2-methyltetrahydrofuran (30 mL) and stirred at elevated temperature for 10 minutes. 40 mL of a 2-methyltetrahydrofuran solution of 2-chloro-4,6-bis((16-methylheptadecyl)oxy)-1,3,5-triazine (3.54 g, 1.0 equivalent, 5.43 mmol) was added dropwise. After the addition was complete, the reaction was stirred for another 1.5 hours. The reaction mixture was then cooled to room temperature and the precipitate was filtered off (G3 sintered glass). The remaining solution was diluted with 600 mL of EE. The organic layer was washed with water (4 × 250 mL) and 0.5 M HCl (250 mL). The organic phase was washed with brine (250 mL). The combined organic phases were dried over MgSO4 and evaporated. The crude product was further purified by MPLC (24g SiO2 column) using a DCM / MeOH gradient elution to obtain the product, which was a colorless waxy substance (1.35g, 1.92mmol, 2-step 35.3%).

[0125] MS (ESI, positive ion): m / z = 704.69 [M+H] +

[0126] (4-((5-((4-((4,6-bis((16-methylheptadecyl)oxy)-1,3,5-triazin-2-yl)amino)butyl) Preparation of (9H-fluorene-9-yl)methyl carbamate (amino)-5-oxopentyl)oxy)-2,6-dimethoxybenzyl)carbamate

[0127]

[0128] Fmoc-PAL (359 mg, 1.0 equivalent, 710 μmol) was dissolved in DMF (4 mL). Then, HOBt dihydrate (146 mg, 1.2 equivalent, 852 μmol) was added and the mixture was cooled to 4 °C. At 4 °C, 4-methylmorpholine (287 mg, 0.32 mL, 4.0 equivalent, 2.84 mmol) was added, followed by EDC HCl (206 mg, 99% wt, 1.5 equivalent, 1.07 mmol) in two portions. N-(4-(λ) 2(-Z-alkyl)butyl)-4,6-bis((16-methylheptadecyl)oxy)-1,3,5-triazine-2-amine (500 mg, 1.0 equivalent, 710 μmol) was dissolved in DMF (3 mL) and added to the mixture. The reaction mixture was stirred at 4 °C for another 5 minutes, then brought to room temperature and stirred at this temperature for 1 hour. After a total stirring time of 3 hours, the mixture was diluted with acetonitrile (8 mL) and cooled to 4 °C. 20 mL of distilled H2O was slowly added at 4 °C, forming an oily precipitate. The precipitate was collected through a P3 sintered glass filter, washed with 100 mL of H2O, dissolved in dichloromethane (100 mL), and washed with brine (100 mL). The organic phase was dried over MgSO4 and the solvent was removed under reduced pressure. The crude product was further purified by MPLC (12g SiO2 column) using a gradient elution of DCM to 80 / 20 DCM / EtOAc to obtain the product, which was a pale yellow oil (702mg, 589μmol, 83.0%).

[0129] MS (ESI, positive ion): m / z = 1191.94 [M+H] +

[0130] 1 H NMR (400MHz, CD2Cl2) δ [ppm] = 7.77 (d, J = 7.6Hz, 2H), 7.60 (d, J = 7.5Hz, 2H), 7.39 (t, J = 7.4Hz, 2H) ,7.30(t,J=7.5Hz,2H),6.14(s,2H),5.81–5.62(m,2H),5.17(s,1H),4.34(d,J=7.1Hz,4H),4.27– 4.13(m,4H),4.06–3.93(m,2H),3.81(s,6H),3.56–3.37(m,2H),3.34–3.19(m,2H),2.32–2.12(m ,2H),2.01(s,1H),1.89–1.74(m,6H),1.66–1.50(m,4H),1.48–1.19(m,56H),0.98–0.74(m,12H).

[0131] 13C NMR (101MHz, CD2Cl2): δ [ppm] = 172.7, 168.8, 160.9, 159.7, 156.5, 144.8, 141.7, 128. 0,127.4,125.5,120.3,107.4,91.6,70.6,68.2,66.8,56.2,54.4,54.3,54.1,54.0,5 3.8,53.8,53.6,53.3,47.8,41.0,39.5,38.1,36.5,34.2,32.4,32.4,32.3,31.6,30.5,30.1,30.1,30.0,29.9,29.8,29.8,29.8,29.3,27.4,27.4,27.2,23.1,22.8,14.3.

[0132] Preparation of 2-chloro-4,6-bis((2-decyltetradecyl)oxy)-1,3,5-triazine

[0133]

[0134] Under a nitrogen atmosphere, 2-decyltetradecyl alcohol (3.85 g, 4.57 mL, 2.0 equivalent, 10.80 mmol) was dissolved in 2-methyltetrahydrofuran (20 mL), cooled to 0 °C, and sodium hydride (2.17 g, 60% wt, 10.0 equivalent, 54.20 mmol) was added in portions. After the addition was complete, the reaction mixture was refluxed for 18 hours. After cooling to -10 °C, the active alcohol was added dropwise to a cooled solution of 2,4,6-trichloro-1,3,5-triazine (1.00 g, 1.0 equivalent, 5.42 mmol) dissolved in 10 mL of 2-methyltetrahydrofuran (-10 °C). The reaction mixture was stirred and warmed to room temperature for 1 hour, then quenched with H₂O and washed with brine (40 mL). The organic phase was dried with MgSO4 and the solvent was removed under vacuum to give 2-chloro-4,6-bis((2-decyltetradecyl)oxy)-1,3,5-triazine.

[0135] MS (ESI, positive ion): m / z = 820.75 [M+H] +

[0136] N 1 Preparation of 1,8-(4,6-bis((2-decyltetradecyl)oxy)-1,3,5-triazin-2-yl)octane-1,8-diamine

[0137]

[0138] Octane-1,8-diamine (7.82 g, 10.0 equivalent, 54.2 mmol) was dissolved in 2-methyltetrahydrofuran (30 mL) and stirred at elevated temperature for 10 minutes. The diamine solution was heated to 70 °C, and a solution of 2-chloro-4,6-di((2-decyltetradecyl)oxy)-1,3,5-triazine (4.45 g, 1.0 equivalent, 5.42 mmol) in 2-methyltetrahydrofuran (40 mL) was added dropwise. The reaction was stirred for about 1.5 hours, then cooled to room temperature and the precipitate was filtered off (G3 sintered glass). The remaining solution was diluted with ethyl acetate (300 mL). The organic layer was washed four times with water (4 × 250 mL), once with 0.5 M HCl (250 mL), and once with brine (250 mL). The combined organic phases were dried over MgSO4 and evaporated. The crude product was further purified by MPLC (24g SiO2 column) using a DCM / MeOH gradient elution to obtain N. 1 -(4,6-bis((2-decyltetradecyl)oxy)-1,3,5-triazin-2-yl)octane-1,8-diamine, as a colorless waxy substance (650 mg, 700 μmol, 2-step 12.9%).

[0139] MS (ESI, positive ion): m / z = 928.88 [M+H] +

[0140] Preparation of 2-(4-(((triisopropylsilyl)oxy)methyl)phenoxy)acetic acid (HMPA-TIPS)

[0141]

[0142] To a suspension of 2-(4-(hydroxymethyl)phenoxy)acetic acid (0.50 g, 1.0 equivalent, 2.70 mmol) in dichloromethane (20 mL), imidazole (0.56 g, 3.0 equivalent, 8.20 mmol) was added, followed by dropwise addition of triisopropylsilyl trifluoromethanesulfonate (2.10 g, 1.80 mL, 2.5 equivalent, 6.90 mmol) at 4 °C. The mixture was warmed to room temperature and stirred for 3 days. Subsequently, the suspension was heated to reflux for 2 hours and the solvent was removed under reduced pressure. The residue was dissolved in THF / H₂O (1:1; 20 mL). Potassium carbonate (0.38 g, 1.0 equivalent, 2.70 mmol) was then added, and the mixture was heated to 50 °C for 1 hour. The reaction mixture was transferred to a separatory funnel and acidified to pH ~3.5 by adding 5 w% citric acid. Ethyl acetate (15 mL) was added, and the phases were separated. The aqueous phase was extracted with ethyl acetate, and the combined organic phases were washed twice with H2O (2 × 20 mL) and once with brine (20 mL). The crude mixture was dried over MgSO4 and the solvent was removed under reduced pressure to give 2-(4-(((triisopropylsilyl)oxy)methyl)phenoxy)acetic acid, which was used directly without further purification.

[0143] 1 H NMR (400MHz, CD2Cl2) δ [ppm] = 7.35–7.26 (m, 2H), 6.93–6.85 (m, 2H), 4.78 (s, 2H), 4.67 (s, 2H), 1.25–1.00 (m, 21H).

[0144] N-(8-((4,6-bis((2-decyltetradecyl)oxy)-1,3,5-triazin-2-yl)amino)octyl)-2-(4- Preparation of (((triisopropylsilyl)oxy)methyl)phenoxy)acetamide

[0145]

[0146] HMPA-TIPS (492 mg, 3.0 equivalent, 1.45 mmol) was dissolved in dichloromethane (8 mL), and HOBt dihydrate (99.5 mg, 1.2 equivalent, 582 μmol) was added. The mixture was cooled to 4 °C. At 4 °C, 4-methylmorpholine (196 mg, 0.22 mL, 4.0 equivalent, 1.94 mmol) was added, followed by EDC HCl (141 mg, 99% wt, 1.5 equivalent, 727 μmol) in two portions. N... 1 -(4,6-bis((2-decyltetradecyl)oxy)-1,3,5-triazin-2-yl)octane-1,8-diamine (450 mg, 1.0 equivalent, 485 μmol) was dissolved in dichloromethane (4 mL) and added to the mixture at 4 °C for 3 minutes. The mixture was stirred for another 5 minutes, brought to room temperature, and stirred at this temperature for 1.5 hours. The mixture was diluted with acetonitrile (3 mL) and distilled H2O (20 mL). The resulting multiphase mixture was transferred to a separatory funnel. 100 mL of brine was added and the aqueous phase was separated. The organic phase was dried over MgSO4 and the solvent was removed under reduced pressure. The crude product was further purified by MPLC (12 g SiO2 column) using gradient elution with DCM / EE to give the product as a pale yellow oil (217 mg, 174 μmol, 35.8%).

[0147] MS (ESI, positive ion): m / z = 1249.15 [M+H] +

[0148] 1H NMR (400MHz, CD2Cl2) δ [ppm] = 7.31 (d, J = 8.9Hz, 2H), 6.91 (d, J = 8.7Hz, 2H), 6.56 (s,2H),4.77(s,2H),4.45(s,2H),4.18(dd,J=25.6,5.9Hz,4H),3.43–3.36(m,2 H),3.34–3.26(m,2H),1.87–1.68(m,2H),1.56(d,J=6.5Hz,4H),1.44–1.30(m,2 8H),1.27(s,60H),1.10(s,12H),1.09(s,6H),1.05(s,3H),0.96–0.81(m,12H).

[0149] 13 C NMR (101MHz, CD2Cl2): δ [ppm] = 172.9, 172.4, 168.8, 168.2, 156.9, 135.9, 127. 9,114.9,70.5,70.3,68.2,65.1,54.4,54.3,54.1,54.0,53.8,53.8,53.6,53. 3,41.4,39.4,38.1,38.1,32.4,31.7,30.5,30.2,30.2,30.1,30.1,30.0,30.0,29.8,29.7,29.7,29.6,28.1,27.3,27.2,23.2,18.3,18.0,14.3,12.8,12.5.

[0150] Example 2: Peptide Synthesis in Solution

[0151] Deprotection

[0152] Dissolve the Fmoc-protected label (1 equivalent) in ethyl acetate (1%). Then add diethylamine (4 equivalents) and stir overnight.

[0153] Dissolve the TIPS-protected label (1 equivalent) in THF (1%). Then add TBAF (2 equivalents) and stir for 2 hours.

[0154] Couplet

[0155] Dissolve the deprotected tag in ethyl acetate (1%). Then add the Fmoc-protected amino acid (Fmoc–AA–OH) (2 equivalents) and Oxyma (2 equivalents) and stir for 1 minute. Then add N,N′-diisopropylcarbodiimide (3 equivalents) and stir overnight.

[0156] extraction

[0157] Transfer the reaction mixture to a separatory funnel and wash with water (10 volume equivalents) and brine (10 volume equivalents). The label is retained in the organic phase and can be used for the next coupling step in solution.

Claims

1. Compound of formula (I) in, X selects freely –O –(CH2) n – A group consisting of n, where n is between 0 and 4. R 1 and R 2 Independent choice of C 11 –C 25 The group consisting of alkyl groups, SPs are spacers, particularly selected from the group consisting of saturated C4–C8 alkyl, unsaturated C4–C8 alkyl, and substituted or unsubstituted C6 aromatic compounds, especially substituted C6 aromatic compounds that are alkyl-substituted C6 aryl groups. Y is a heteroatom, specifically chosen from the group consisting of –O– and –NH–. L is the peptide synthesis linker, and m can be 0 or 1, especially m can be 1.

2. The compound according to any of the preceding claims, wherein n is 0.

3. The compound according to claim 1 or 2, wherein R 1 and R 2 They are independent of each other as branches or replace C. 11 –C 25 alkyl.

4. The compound according to any of the preceding claims, wherein R 1 and R 2 Independent choice of C 13 –C 25 A group composed of alkyl groups.

5. The compound according to any of the preceding claims, wherein R 1 Choose C freely 17 –C 25 A group composed of alkyl groups.

6. The compound according to any of the preceding claims, wherein R 2 Choose C freely 17 –C 25 A group composed of alkyl groups.

7. The compound according to any of the preceding claims, wherein Y1 is –NH– and Y2 is –NH– or O.

8. The compound according to any of the preceding claims, wherein Y1 is –NH– and Y2 is –NH–.

9. The compound according to any of the preceding claims, wherein SP is selected from the group consisting of saturated C4–C8 alkyl, unsaturated C4–C8 alkyl, and substituted C6 aromatic compounds.

10. The compound according to any of the preceding claims, wherein SP is selected from the group consisting of saturated C4–C8 alkyl compounds and substituted C6 aromatic compounds.

11. The compound according to any of the preceding claims, wherein SP is selected from the group consisting of C4–C8 alkyl groups.

12. The compound according to any of the preceding claims, wherein the connector L is selected from Rink, Sieber, triphenylmethyl, Ramage, Wang, Sasrin, HMPB, 2-chlorotriphenylmethyl, MBHA, PAL, HMBA and HMPA.

13. The compound according to any of the preceding claims, wherein the connector L is selected from Ramage, Rink, HMPA, PAL and HMBA.

14. The compound according to claims 1 to 11, wherein the connector L is selected from Rink, Sieber, triphenylmethyl, Ramage, Wang, Sasrin, HMPB, 2-chlorotriphenylmethyl and MBHA.

15. The compound according to claim 14, wherein the connector L is selected from Rink, Sieber and triphenylmethyl.

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