Oxime-bonded glycosyl thioether as well as preparation method and application thereof

Abstract

The invention belongs to the field of chemical synthesis, and relates to glycosyl thioether with oxime functional groups and a preparation method and application thereof. According to the invention, glycosyl thioether with oxime functional groups is prepared, the glycosyl thioether is used as a glycosyl free radical donor, a styrene compound is used as a glycosyl acceptor substrate, and a method for synthesizing alkyl C-glycoside through visible light catalysis is established and is used for synthesizing a series of C-glycoside compounds. The oxime-bonded glycosyl thioether prepared by the invention is stable in property, the preparation method has the advantages of simplicity, convenience, high yield, wide applicable saccharide range and the like, and the oxime-bonded glycosyl thioether is applied to synthesis of carbon glycoside and has the advantages of simplicity, wide substrate application range, including various drugs and polypeptides and the like. Therefore, the glycosyl thioether provides a new thought for development of complex glycoconjugates and drugs, and further promotes industrial development of carbon glycoside medicines.

Description

Technical Field

[0001] This invention belongs to the field of chemical synthesis, specifically relating to oxime glycosyl thioethers, their preparation methods, and uses. Background Technology

[0002] Glycosides play important roles in pharmaceuticals, food, surfactants, and cosmetics. Alkyl C-glycosides are a type of glycoside, specifically referring to compounds in which the carbon atom of the glycosyl group is directly bonded to the carbon atom of the aglycone. These compounds are widely found in natural products and drug molecules, exhibiting high biological activity and good in vivo metabolic stability. Due to their broad application value, research on the synthesis of alkyl C-glycosides is of great significance.

[0003] The most important current method for synthesizing alkyl C-glycosides via glycosyl radicals is the addition of glycosyl radicals to electron-deficient alkenes. Currently, the widely used glycosyl radical donor is glycosyl bromide, but it has poor stability and is extremely unstable at room temperature, which is detrimental to industrial production.

[0004] Studies have reported that glycosyl thioethers can be used as free radical precursors to generate glycosyl radicals via photocatalysis or copper catalysis, which then participate in glycosylation reactions. Therefore, glycosyl thioethers can act as glycosyl radical donors, activating to generate glycosyl oxonium or glycosyl thionium, which then react with nucleophiles to form glycosidic bonds. Several advantages exist in this reaction: glycosyl thioethers provide good stereoselectivity, improving reactivity and stability, and exhibit good functional group compatibility, making them significant for the synthesis of complex glycoconjugates and drug development. However, there are currently few reports on the use of glycosyl thioethers as glycosyl radical donors for the synthesis of corresponding glycosides, and these studies suffer from drawbacks such as narrow substrate scope and low yields.

[0005] In summary, current methods for synthesizing alkyl C-glycosides via glycosyl radicals have some problems, such as poor stability of glycosyl radical donors, narrow substrate range, and low yield. Summary of the Invention

[0006] In view of the prior art, this invention designs and synthesizes a glycosyl thioether with an oxime functional group and applies it to the synthesis of alkyl C-glycosides.

[0007] This invention provides a compound of formula I, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a solvate thereof, or a crystal form thereof, wherein the compound has the following structural formula:

[0008]

[0009] Among them, the sugar is selected from monosaccharides protected by hydroxyl groups;

[0010] The hydroxyl protecting group is selected from at least one of ether protecting groups, ester protecting groups, acetal protecting groups, benzylidene protecting groups, or acetone protecting groups.

[0011] Preferably, the monosaccharide is selected from substituted or unsubstituted monosaccharides, and the substituent is selected from methyl, methoxy, and C6 aryl groups;

[0012] And / or, the hydroxyl protecting group is selected from at least one of acetyl, tert-butyldiphenylsilane ether, acetone ide, and benzyl ide protecting groups.

[0013] Preferably, the compound shown in Formula I has the following structural formula:

[0014]

[0015] The present invention provides a method for preparing the compound represented by Formula I above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a solvate thereof, or a crystal form thereof, comprising the following steps:

[0016]

[0017] Step 1: Compound 1 reacts with a reducing agent in the presence of a co-catalyst to obtain compound 2;

[0018] Step 2: Add an alkali and an acylation reagent to compound 2, and stir to obtain the final product.

[0019] Preferably, the co-catalyst is sodium acetate, the reducing agent is hydroxylamine hydrochloride, and the reaction is carried out in a mixed solvent of ethanol / water with a volume ratio of 1-4:1, under reflux at 98-102°C for 4-8 hours.

[0020] And / or, the base is triethylamine or pyridine, and the acylation reagent is trifluoromethylbenzoyl chloride; the stirring is carried out at 0-4°C for 1-2 hours.

[0021] Preferably, compound 1 is prepared by steps comprising at least one of the following six pathways:

[0022] Route 1: Add a reducing agent and a Lewis acid catalyst to a monosaccharide protected by all hydroxyl groups, and react at 20-25℃ to obtain the product;

[0023] Route 2 involves adding a strong base catalyst and a brominated monosaccharide to the reducing agent and reacting it at 20-25°C to obtain the product.

[0024] Route 3: The compound obtained by any one of routes 1 and 2 is mixed with a strong base and reacted at 20-25℃ for 20-30 minutes. A neutralizing agent is added, the pH is adjusted to 5-7, filtered, and the filtrate is reacted with a monohydroxyl protecting agent at 20-25℃ to obtain the final product.

[0025] The following paths can be selected according to the type of raw sugar:

[0026] Route 4: The compound prepared by any one of routes 1 or 2 of the six-membered ring monosaccharide with full hydroxyl protection is mixed with a strong base and reacted at 20-25°C for 20-30 minutes. A neutralizing agent is added, the pH is adjusted to 5-7, filtered, and the filtrate is reacted with a dihydroxyl protecting agent at 20-25°C to obtain the product.

[0027] Route 5: The compound obtained by preparing the five-membered ring monosaccharide with all-hydroxyl protection according to the steps described in Route 4 is mixed with an organic base catalyst, and after adding an acetylation reagent, it is reacted at 20-25°C to obtain the product.

[0028] Route 6: A monosaccharide with one exposed hydroxyl group is mixed with an organic base catalyst, and an acetylation reagent is added. The mixture is then reacted at 20-25°C for 6-10 hours. A bromination reagent is added to the product, and the mixture is reacted at 20-25°C for 5-8 hours to obtain a brominated monosaccharide. The process is then repeated according to the steps of Route 2 to obtain the final product.

[0029] The reducing agent is 2-mercaptoacetophenone, the Lewis acid catalyst is boron trifluoride diethyl ether, the strong base catalyst is potassium tert-butoxide, the strong base is sodium methoxide or triethylamine, the neutralizing agent is Amberlite H+ resin, the organic base catalyst is 4-dimethylaminopyridine, the acetylation agent is acetic anhydride, and the bromination agent is trimethylbromosilane.

[0030] The monohydroxyl protecting agent is selected from tert-butyldiphenylchlorosilane, trimethylchlorosilane, triethylchlorosilane, triisopropylchlorosilane, tert-butyldimethylchlorosilane, triphenylmethyl ether, and tetrahydropyran; the dihydroxyl protecting agent is 2,2-dimethoxypropane and benzaldehyde dimethyl acetal.

[0031] The present invention provides the use of the compound of Formula I above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a solvate thereof, or a crystal form thereof, for the preparation of glycoside compounds and / or glycoside drugs and / or glycoside vaccines.

[0032] The present invention also provides a compound of formula II, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a solvate thereof, or a crystal form thereof, having the following structural formula:

[0033]

[0034] The sugar is selected from monosaccharides protected by hydroxyl groups.

[0035] The hydroxyl protecting group is selected from at least one of ether protecting groups, ester protecting groups, acetal protecting groups, benzylidene protecting groups, or acetone protecting groups;

[0036] Ar is selected from C6-C that is substituted with 1-3 R1 atoms or is unsubstituted.10 Aromatic rings, 5-9 membered aromatic heterocycles substituted with or unsubstituted with 1-3 R1 groups, and C2 alkenyl groups substituted with or unsubstituted with 1-3 R1 groups;

[0037] R1 is independently selected from C6-C6. 10 Aromatic rings, C1-C 10 Alkyl, C1-C 10 alcohols, C1-C 10 Alkoxy, C6-C 10 aryloxy group, substituted or unsubstituted C2-C 10 Ester group, substituted or unsubstituted C2-C 10 Amide, C1-C 10 Alkylthio, halogen, substituted C2 boron ester, substituted or unsubstituted C1-C 10 Acyl groups, substituted C2-olefin groups, N-protected oligopeptides, and drug molecules;

[0038] Alternatively, two R1s may be linked together to form substituted or unsubstituted 5-9 membered heterocyclic alkyl groups;

[0039] The substituents are selected from 5-9 membered aromatic heterocycles, N-protected 5-9 membered heterocycles, N-protected amino groups, and C1-C... 10 Alkyl, C6-C 10 Aromatic rings;

[0040] The drug molecule is selected from carboxyl-containing drugs and halogen-substituted C6-C drugs. 10 Aromatic ring drugs, hydroxyl-substituted C6-C 10 Aromatic ring drugs.

[0041] Preferably, R1 is

[0042] L1 is selected from hydrogen, C1-C10 alkyl, C1-C10 alcohol, C6-C10 methylphenol, C1-C10 alkylthio, C1-C10 ester, C6-C10 arylmethyl, and C5-C9 aromatic heterocyclic methyl.

[0043] Preferably, the compound shown in Formula II has the following structural formula:

[0044]

[0045]

[0046]

[0047]

[0048] The present invention also provides a method for preparing the compound represented by Formula II above, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a solvate thereof, or a crystal form thereof, comprising the following steps:

[0049]

[0050] By mixing raw material A and raw material B, we obtain...

[0051] Among them, sugar, Ar, and R1 are as described in any of the above items.

[0052] Preferably, the specific steps include the following:

[0053] At 20-25℃, raw material A is mixed with catalyst and raw material B, and reacted under 450-460nm light for 3-6 hours to obtain the product; the catalyst is Ir(ppy)3.

[0054] This invention establishes a visible-light-catalyzed method for the synthesis of β-carbonyl-α-alkyl C-glycosides using oxime-containing glycosyl thioethers as glycosyl radical donors and styrene compounds as glycosyl acceptor substrates, resulting in the synthesis of a series of C-glycoside compounds. The oxime-containing glycosyl thioethers prepared by this invention are stable, and their preparation method is simple, has high yield, and is applicable to a wide range of sugars. Applying this method to the synthesis of C-glycosides offers advantages such as simplicity and broad substrate compatibility. This indicates that the glycosyl thioether provides a new approach for the development of complex glycoconjugates and drugs, further promoting the industrialization of C-glycoside pharmaceuticals.

[0055] The compounds and derivatives provided in this invention can be named according to the IUPAC (International Union of Pure and Applied Chemistry) or CAS (Chemical Abstracts Service, Columbus, OH) nomenclature system.

[0056] Regarding the definition of terms used in this invention: Unless otherwise stated, the initial definitions provided for groups or terms herein apply to the groups or terms used throughout this specification; for terms not specifically defined herein, the meanings that a person skilled in the art would give them should be given based on the disclosure and context.

[0057] "Substitution" refers to the replacement of hydrogen atoms in a molecule by other different atoms or molecules.

[0058] The minimum and maximum carbon atom content in hydrocarbon groups are indicated by a prefix, for example, the prefix C. a～b Alkyl indicates any alkyl group containing "a" to "b" carbon atoms. Therefore, for example, "C 1～4 "Alkyl" refers to an alkyl group containing 1 to 4 carbon atoms.

[0059] "Alkyl" refers to a saturated hydrocarbon chain having a specified number of member atoms. For example, C1-C6 alkyl refers to an alkyl group having 1 to 6 member atoms, such as 1 to 4 member atoms. Alkyl groups can be straight-chain or branched. Representative branched alkyl groups have one, two, or three branches. Alkyl groups may optionally be substituted by one or more substituents as defined herein. Alkyl groups include methyl, ethyl, propyl (n-propyl and isopropyl), butyl (n-butyl, isobutyl, and tert-butyl), pentyl (n-pentyl, isopentyl, and neopentyl), and hexyl. Alkyl groups may also be part of other groups, such as C1-C6 alkoxy groups.

[0060] “R a R b "Connected to form a ring" refers to R a and R b At least one atom in each is connected by a chemical bond, such that R a R b Together with the molecular backbone structure in which they reside, they form a ring structure.

[0061] "Halogen" refers to fluorine, chlorine, bromine, or iodine.

[0062] An "aromatic ring" refers to an aromatic unsaturated ring consisting of one or two rings with a specified number of member atoms. When there are two rings, the two rings share at least two atoms, for example, "C6~C6". 10 "Aromatic ring" refers to an aromatic unsaturated ring containing 6 to 10 carbon atoms; It is a kind of "C" 10 "Fragrant ring".

[0063] "Aromatic heterocycle" refers to an aromatic unsaturated ring containing at least one heteroatom and having a single or two rings. When there are two rings, the two rings share at least two atoms, where the heteroatom refers to a nitrogen atom, an oxygen atom, or a sulfur atom. For example... It is an "S-containing C5 aromatic heterocyclic ring". It is a "C9 aromatic ring containing O". It is an "S-containing C9 aromatic ring".

[0064] "Heterocyclic" or "heterocyclic alkyl" refers to a saturated ring or a non-aromatic unsaturated ring containing at least one heteroatom and having a single ring; where heteroatoms refer to nitrogen, oxygen, sulfur, or boron atoms.

[0065] "Arylmethyl" refers to an aryl group that is linked to a linkage site via a methylene group, for example... It is a C6 arylmethyl group.

[0066] "Aromatic heterocyclic methyl" refers to a group in an aromatic heterocycle that is connected to a linking site via a methylene group, for example... It is a C9 aromatic heterocyclic methyl group.

[0067] "Alkenyl" refers to an unsaturated alkane chain containing at least one double bond.

[0068] "Alcohol" refers to a saturated alkane chain containing at least one hydroxyl group.

[0069] "Methylphenol" refers to a group containing at least one hydroxyl group linked to an aromatic ring, with the aromatic ring linked to the linkage site via a methyl group. For example, It is a C6 methylphenol.

[0070] "Alkoxy" refers to an alkyl group that is connected to a bonding site through an oxygen atom. Its alkane chain can be a saturated alkane chain or a non-aromatic unsaturated alkane chain containing at least one double bond. For example, methoxy refers to -OCH3.

[0071] "Alkylthio" refers to a group in which an alkyl group is attached to a linking site via a sulfur atom. For example, methylthio is -SCH3.

[0072] "Aryloxy group" refers to a group on an aromatic ring that is connected to a linking site through an oxygen atom. For example, phenoxy group refers to -OPh.

[0073] "Ester group" refers to a group containing at least one ester group. Saturated alkane chains, such as the C2 ester group, are

[0074] "Amide" refers to a substance containing at least one Saturated alkane chains, such as C2 amides, are

[0075] "Acyl" refers to a saturated alkane chain containing at least one carbonyl group, where the atom attached to the bond site is a carbon atom from the carbonyl group; for example, a C1 acyl group is...

[0076] "Boron-ester bond" refers to the bond formed by alkane chains. The group attached to the linkage site, such as a C2 borosilicate, is

[0077] "Oligopeptide" refers to a compound consisting of 2 to 9 amino acids linked by amide bonds.

[0078] In this invention, "hydroxyl protection" refers to the attachment of an oxygen atom (O) to a protecting group. The protecting group represents a functional group that, when attached to the oxygen atom in a hydroxyl group, prevents interference with the hydroxyl group. Protecting groups include ether protecting groups, ester protecting groups, acetal protecting groups, benzyl protecting groups, and acetone protecting groups.

[0079] "N protection" means that N is attached to a protecting group, which includes Boc and Fmoc. "Boc" refers to tert-butyloxycarbonyl, and "Fmoc" refers to fluorenemethyloxycarbonyl.

[0080] The term "pharmaceutically acceptable" means that a carrier, delivery substance, diluent, excipient, and / or the salt formed therefrom is generally chemically or physically compatible with other components constituting a drug dosage form and physiologically compatible with receptors.

[0081] The terms "salt" and "pharmaceutical salt" refer to acidic and / or basic salts formed by the above-described compounds or their stereoisomers with inorganic and / or organic acids and bases, including zwitterionic salts (internal salts) and quaternary ammonium salts, such as alkylammonium salts. These salts can be obtained directly during the final separation and purification of the compounds. Alternatively, they can be obtained by mixing the above-described compounds or their stereoisomers with an appropriate amount (e.g., equimolar amounts) of an acid or base. These salts may be obtained by precipitating in solution and collecting by filtration, by recovery after solvent evaporation, or by freeze-drying after reaction in an aqueous medium. The salts described in this invention can be hydrochlorides, sulfates, citrates, benzenesulfonates, hydrobromides, hydrofluoric acids, phosphates, acetates, propionates, succinates, oxalates, malates, succinates, fumarates, maleates, tartrates, or trifluoroacetates of the compounds.

[0082] Obviously, based on the above description of the present invention, and according to common technical knowledge and conventional methods in the field, various other modifications, substitutions, or alterations can be made without departing from the basic technical concept of the present invention.

[0083] The following detailed embodiments further illustrate the above-described content of the present invention. However, this should not be construed as limiting the scope of the present invention to the following examples. All technologies implemented based on the above-described content of the present invention fall within the scope of the present invention. Detailed Implementation

[0084] Unless otherwise specified, all reagents and materials used in the following examples and experimental cases are commercially available.

[0085] Fully acetyl-protected rhamnose and fucose are obtained by acetylation of commercially available rhamnose and fucose, respectively, through the following steps:

[0086] In a round-bottom flask equipped with a magnetic stirrer, fucose or rhamnose (1.0 eq., 9.14 mmol) and 4-dimethylaminopyridine (0.1 eq., 0.91 mmol) were added, followed by 10 mL of pyridine (reaction concentration: 1 M). The flask was stoppered with a rubber stopper and placed in an ice-water bath to cool to 0 °C. Acetic anhydride (10.0 eq., 91.40 mmol, 8.6 mL) was slowly added dropwise. After the addition was complete, the ice-water bath was removed, and stirring was continued at room temperature until the sugar starting material was completely consumed (TLC monitoring). After the reaction was complete, the reaction mixture was transferred to a 250 mL separatory funnel, diluted with 100 mL of ethyl acetate, and washed six times with 100 mL of 10% citric acid aqueous solution. The organic phase was washed with 100 mL of saturated brine, separated, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to obtain fully acetyl-protected fucose or fully acetyl-protected rhamnose.

[0087] The brominated raw sugar is obtained by bromination of 2-deoxy-2-glucosamine protected by a fully acetyl group, and the specific steps are as follows:

[0088] In a round-bottom flask equipped with a magnetic stirrer, 1.0 eq. (2.57 mmol, 1.0 g) of fully acetyl-protected 2-deoxy-2-glucosamine and 10 mL of dry dichloromethane were added. The flask was stoppered with a rubber stopper and placed in an ice-water bath to cool to 0°C. A solution of hydrobromic acid in acetic acid (10.0 eq., 25.7 mmol, 1.4 mL) was slowly added dropwise. After the addition was complete, the ice-water bath was removed, and stirring continued at room temperature until the sugar starting material was completely consumed (TLC monitoring). After the reaction was complete, the reaction mixture was transferred to a 250 mL separatory funnel, diluted with 100 mL of dichloromethane, and washed once with 100 mL of water, followed by twice with 100 mL of saturated sodium bicarbonate solution. The organic phase was then washed with 100 mL of saturated brine, separated, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to obtain a 1-hour brominated sugar starting material.

[0089] The structure of the compound was determined by 1H NMR spectroscopy (NMR spectroscopy). 1 It was determined by H NMR. 1 The H NMR measurements were performed using a 400 MHz NMR spectrometer with deuterated trichloromethane (CDCl3) as the solvent.

[0090] Example 1: Oxime glycosyl thioethers and their preparation method

[0091] This embodiment provides a glycosyl thioether, the preparation method of which includes the following steps:

[0092]

[0093] I. Synthesis of Compound 3

[0094] (1) Synthesis of Compound 1

[0095] In a round-bottom flask equipped with a magnetic stirrer, add 1.0 eq. (15.37 mmol, 6.0 g) of fully acetyl-protected starting sugar. In a glove box (nitrogen atmosphere), add 30 mL of dry dichloromethane (0.5 M reaction concentration) and stopper with a rubber stopper. Place the flask in an ice-water bath and cool to 0°C. Insert a nitrogen balloon and slowly add 1.5 eq. (23.06 mmol, 3.51 g) of 2-mercaptoacetone. After stirring for 10 minutes, slowly add 5.0 eq. (76.86 mmol, 9.5 mL) of boron trifluoride ether. After the addition is complete, remove the ice-water bath and continue stirring at room temperature until the sugar starting sugar is completely consumed (TLC monitoring, reaction time approximately 12–18 hours). After the reaction is complete, place the flask in an ice-water bath and cool to 0°C. Slowly add 20 mL of triethylamine to quench excess boron trifluoride ether. Next, the mixture was concentrated under reduced pressure, and the residue was separated and purified by column chromatography to obtain the final product.

[0096] (2) Synthesis of Compound 2

[0097] In a round-bottom flask equipped with a magnetic stirrer, compound 1 (1.0 eq., 7.46 mmol, 3.6 g), hydroxylamine hydrochloride (1.5 eq., 2.28 mmol, 778 mg), and anhydrous sodium acetate (2.0 eq., 14.92 mmol, 1.22 g) were added. Then, 40 mL of a 1:1 mixture of ethanol and water was added. The reaction mixture was placed in an oil bath at 100 °C and heated under reflux until compound 1 was completely consumed (TLC monitoring, reaction time approximately 4–8 hours). Subsequently, the mixture was distilled under reduced pressure to remove most of the ethanol from the reaction mixture, and then diluted with 50 mL of water. The aqueous phase was transferred to a 125 mL separatory funnel and extracted three times with 50 mL of ethyl acetate. The combined organic phases were dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain the final product.

[0098] (3) Synthesis of compound 3

[0099] Compound 2 (1.0 eq., 6.43 mmol, 3.2 g) and 15 mL of dry dichloromethane were added to a round-bottom flask equipped with a magnetic stirrer. The flask was stoppered with a rubber stopper and placed in an ice-water bath to cool to 0 °C. Triethylamine (1.5 eq., 9.65 mmol, 1.34 mL) was added dropwise. After stirring for 5 minutes, p-trifluoromethylbenzoyl chloride (1.2 eq., 7.72 mmol, 1.15 mL) was slowly added dropwise. Stirring continued until compound 2 was completely consumed (TLC monitoring, reaction time approximately 1–2 hours). After the reaction was complete, the reaction solution was transferred to a 250 mL separatory funnel and diluted with 100 mL of ethyl acetate. The organic phase was washed three times with an equal volume of saturated sodium bicarbonate aqueous solution, dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain the final product.

[0100] II. Structure and Characterization of Compounds

[0101] (1) Compound 1a

[0102] 3H),2.17(s,3H),2.05(s,3H),2.03(s,3H),2.01(s,3H).

[0103] (2) Compound 2a

[0104] The yield was 70%. Structural characterization data are as follows: 1 H NMR (CDCl3, 400)

[0105]

[0106] (3) Compound 3a

[0107] (CDCl3, 400 MHz) δ: 8.25 (d, J = 8.0 Hz, 2H), 7.77 (d, J = 8.2 Hz, 2H), 7.65 (tt, J = 4.8, 2.6 Hz, 1H), 7.45 - 7.36 (m, 3H), 5.61 (d, J = 1.5 Hz, 1H), 5.46 (dd, J = 3.3, 1.5 Hz, 1H), 5.33 (t, J = 9.9 Hz, 1H), 5.26 (dd, J = 10.0, 3.3 Hz, 1H), 4.54 (ddd, J = 9.8, 5.6, 2.5 Hz, 1H), 4.32 (dd, J = 12.2, 5.6 Hz, 1H), 4.12 (dd, J = 12.3, 2.5 Hz, 1H), 2.52 (s, 3H), 2.14 (s, 3H), 2.07 (s, 3H), 2.06 (s, 3H), 1.98 (s, 3H). (2R,3R,4S,5S,6R)-2-(acetoxymethyl)-6-((2-(1-(((4-(trifluoromethyl)benzoyl)oxy)imino)ethyl)phenyl)thio)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0108] (4) Compound 1b

[0109] 2.00 (s, 3H), 1.23 (d, J = 6.2 Hz, 3H).

[0110] (5) Compound 2b

[0111] 3.4 Hz, 1H), 5.05 (t, J = 9.8 Hz, 1H), 4.32 - 4.19 (m, 1H), 2.18 (s, 2.4H), 2.12 (s, 0.6H), 2.07 (s, 2.4H), 2.05 (s, 0.6H), 2.00 (s, 3H), 1.94 (s, 3H),​​​​​​3.3Hz,1H),5.12(t,J=9.9Hz,1H),4.34(dq,J=9.5,6.1Hz,1H),2.52(s, 3H),2.12(s,3H),2.05(s,3H),1.97(s,3H),1.24(d,J=6.3Hz,3H).(2S, 3R,4R,5S,6S)-2-methyl-6-((2-(1-(((4-(trifluoromethyl)benzoyl)oxy)imino)ethyl)phenyl)thio)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0114] (7) Compound 1c

[0115] Hz,1H) ,3.87(q,J=6.5Hz,1H),2.58(s,3H),2.17(s,3H),2.01(s,3H),1.96(s,3H),1.23(d,J=6.4Hz,3H).

[0116] (8) Compound 2c

[0117] MHz)δ:8.78(s,1H),7.78-7.47(m,1H),7.50-7.00(m,3H),5.29-5.18(m,2H),5.03(dd,J=10.0,3.4Hz,1H), 4.64(d,J=10.1Hz,1H) ,3.77(q,J=6.4Hz,1H),2.22(s,3H),2.19(s,3H),2.07(s,3H),1.98(s,3H),1.21(d,J=6.4Hz,3H).

[0118] (9) Compound 3c

[0119]

[0120] 5.06 (dd, J = 9.9, 3.4 Hz, 1H), 4.80(d,J=10.1Hz,1H) , 3.79 (q, J = 6.4 Hz, 1H), 2.51 (s, 3H), 2.16 (s, 3H), 1.97 (s, 3H), 1.94 (s, 3H), 1.15 (d, J = 6.4 Hz, 3H). (2S,3R,4R,5S,6S)-2-methyl-6-((2-(1-(((4-(trifluoromethyl)benzoyl)oxy)imino)ethyl)phenyl)thio)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0121] (10) Compound 1d

[0122] (dd, J = 5.2, 4.0 Hz, 0.8H), 5.30 (t, J = 5.5 Hz, 0.8H), 5.23 (t, J = 5.9 Hz, 0.2H), 4.42 (ddd, J = 5.9, 4.0, 3.0 Hz, 0.2H), 4.38 - 4.26 (m, 1.8H), 4.20 (dd, J = 12.2, 4.1 Hz, 0.2H), 4.11 (dd, J = 13.0, 4.9 Hz, 0.8H), 2.57 (s, 2.4H), 2.56 (s, 0.6H), 2.13 (s, 0.6H), 2.10 (s, 0.6H), 2.07 (s, 2.4H), 2.06 (s, 0.6H), 2.06 (s, 2.4H), 2.05 (s, 2.4H).

[0123] (11) Compound 2d

[0124] 4.3 Hz, 1H), 2.23 (s, 3H), 2.08 (s, 3H), 2.07 (s, 3H), 2.06 (s, 3H).

[0125] (12) Compound 3d

[0126] Hz, 1H), 4.24 (q, J = 4.1 Hz, 1H), 4.09 (dd, J = 12.0, 4.3 Hz, 1H), 2.47 (s, 3H), 2.03 (s, 3H), 2.00 (s, 3H), 1.98 (s, 3H). (2R,3R,4R,5R)-2-(acetoxymethyl)-5-((2-(1-(((4-(trifluoromethyl)benzoyl)oxy)imino)ethyl)phenyl)thio)tetrahydrofuran-3,4-diyldiacetate

[0127] Example 2: Oxime glycosyl thioethers and their preparation method

[0128] This embodiment provides a glycosyl thioether, the preparation method of which includes the following steps:

[0129]

[0130] I. Synthesis of Compound 3

[0131] (1) Synthesis of Compound 1

[0132] In a round-bottom flask equipped with a magnetic stirrer, add 1.2 eq. (12.00 mmol, 1.83 g) of 2-mercaptoacetone and 10 mL of dry tetrahydrofuran (reaction concentration: 0.5 M). At room temperature, add potassium tert-butoxide (1.2 eq. (12.00 mmol, 1.35 g) and stopper the flask. After stirring for 30 minutes, place the flask in an ice-water bath and cool to 0°C. Slowly add 10 mL of a dry tetrahydrofuran solution of the brominated sugar (1.0 eq. (10.00 mmol, 4.11 g). After the addition is complete, remove the ice-water bath and continue stirring at room temperature until the sugar is completely consumed (TLC monitoring, reaction time approximately 6–10 hours). After the reaction is complete, transfer the reaction mixture to a 250 mL separatory funnel, dilute with 100 mL of ethyl acetate, and wash the organic phase three times with 100 mL of water. The organic phase was washed with 100 mL of saturated saline solution, dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain the final product.

[0133] (2) Synthesis of Compound 2

[0134] Follow the method of step (2) in Example 1.

[0135] (3) Synthesis of compound 3

[0136] Follow the method of step (3) in Example 1.

[0137] II. Structure and Characterization of Compounds

[0138] (1) Compound 1e

[0139] 2H),4.82(d,J=10.1Hz,1H),4.22(dd,J=12.3,5.6Hz,1H),4.15(dd,J=12.3,2.6Hz,1H), 3.78(ddd,J=10.1,5.6,2.5Hz,1H),2.59(s,3H),2.07(s,3H),2.03(s,6H),1.99(s,3H).

[0140] (2) Compound 2e

[0141] 1H), 4.12 (dd, J=12.3, 2.5Hz, 1H), 3.65 (ddd, J=10.0, 5.4, 2.4Hz, 1H), 2.21 (s, 3H), 2.07 (s, 3H), 2.06 (s, 3H), 2.00 (s, 3H), 1.99 (s, 3H).

[0142] Configuration 2: 8.02(s,1H),7.69(d,J=7.8Hz,1H),7.41(t,J=7.6Hz,1H),7.33(td,J=7.7,1. 7Hz,1H),7.16(dd,J=7.5,1.5Hz,1H),5.18(t,J=9.3Hz,1H),5.05(q,J=9.8Hz,2H), 4.73(d,J=10.2Hz,1H) ,4.20(dd,J=12.2,5.5Hz,1H),4.11(dd,J=12.0,2.6Hz,1H),3.72-3.50(m ,1H),2.15(s,3H),2.09(s,3H),2.06(s,3H),2.002(s,3H),1.999(s,3H).

[0143] (3) Compound 3e

[0144] 2H),7.78(d,J=8.2Hz,2H),7.72-7.63(m,1H),7.45-7.36(m,3H),5.24(t,J=9.3Hz,1H),5.12-4.99(m,2H),4 .86(d,J=10.2Hz,1H),4.21(dd,J=12.3,5.2Hz,1H),4.07(dd,J=12.3,2.3Hz,1H),3.67(ddd,J=10.1,5.2,2.3 Hz,1H),2.50(s,3H),2.01(s,6H),1.97(s,3H),1.95(s,3H).(2R,3R,4S,5S,6R)-2-(acetoxymethyl)-6-((2- (1-(((4-(trifluoromethyl)benzoyl)oxy)imino)ethyl)phenyl)thio)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0145] (4) Compound 3e'

[0146] (m, 2H), 4.42 (dd, J = 10.4, 4.9 Hz, 1H), 3.88 (t, J = 8.9 Hz, 1H), 3.79 (t, J = 10.1 Hz, 1H), 3.56 (td, J = 9.7, 4.9 Hz, 1H), 3.45 (t, J = 9.4 Hz, 1H), 3.34 - 3.26 (m, 1H), 2.52 (s, 3H). 1-(2-(((2R,4aR,6S,7R,8R,8aS)-7,8-dihydroxy-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-6-yl)thio)phenyl)ethan-1-one O-(4-(trifluoromethyl)benzoyl)oxime

[0147] (5) Compound 1f

[0148] 4.11 (m, 2H), 3.98 (t, J = 6.6 Hz, 1H), 2.56 (s, 3H), 2.12 (s, 3H), 2.01 (s, 3H), 2.00 (s, 3H), 1.94 (s, 3H).

[0149] (6) Compound 2f

[0150] 4.20 (dd, J = 11.3, 7.1 Hz, 1H), 4.10 (dd, J = 11.3, 6.2 Hz, 1H), 3.89 (t, J = 6.6 Hz, 1H), 2.21 (s, 3H), 2.17 (s, 3H), 2.07 (s, 3H), 2.03 (s, 3H), 1.98 (s, 3H).

[0151] (7) Compound 3f

[0152] 1H), 5.26 (t, J = 10.0 Hz, 1H), 5.08 (dd, J = 9.9, 3.4 Hz, 1H), 4 .86(d,J=10.1Hz,1H) , 4.13 (dd, J = 11.3, 6.9 Hz, 1H), 4.06 (dd, J = 11.3, 6.3 Hz, 1H), 3.94 - 3.86 (m, 1H), 2.50 (s, 3H), 2.15 (s, 3H), 1.965 (s, 3H), 1.958 (s, 3H), 1.95 (s, 3H). (2R,3R,4S,5S,6R)-2-(acetoxymethyl)-6-((2-(1-(((4-(trifluoromethyl)benzoyl)oxy)imino)ethyl)phenyl)thio)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0153] (8) Compound 1g

[0154] 4.08 (d, J = 9.5 Hz, 1H), 3.72 (s, 3H), 2.56 (s, 3H), 1.99 (s, 6H), 1.98 (s, 3H).

[0155] (9) Compound 2g

[0156] (s, 3H), 2.05 (s, 3H), 1.99 (s, 3H), 1.98 (s, 3H).

[0157] (10) Compound 3g

[0158] 1H), 5.17 (t, J = 9.7 Hz, 1H), 5.04 (t, J = 9.6 Hz, 1H), 4.91(d,J=10.2Hz,1H) , 3.98 (d, J = 10.0 Hz, 1H), 3.61 (s, 3H), 2.51 (s, 3H), 1.99 (s, 3H), 1.98 (s, 3H), 1.96 (s, 3H). (2S,3S,4S,5R,6S)-2-(methoxycarbonyl)-6-((2-(1-(((4-(trifluoromethyl)benzoyl)oxy)imino)ethyl)phenyl)thio)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0159] (11) Compound 1h

[0160] 4.20(dd,J=12.2,5.6Hz,1H),4.11(dd,J=12.2,2.3Hz,1H),3.88(td,J=10.3,8.6Hz,1H),3.77( ddd,J=10.1,5.6,2.4Hz,1H),2.57(s,3H),2.05(s,3H),2.01(s,3H),2.00(s,3H),1.92(s,3H).

[0161] (12) Compound 2h

[0162] 1H),4.19(dd,J=12.3,5.4Hz,1H),4.08(dd,J=12.3,2.4Hz,1H),4.05-3.97(m,1H),3.59(ddd ,J=10.1,5.4,2.4Hz,1H),2.22(s,3H),2.05(s,3H),2.01(s,3H),1.983(s,3H),1.976(s,3H).

[0163] (13) Compound 3h

[0164] J=9.3Hz,1H),5.28(t,J=9.7Hz,1H),5.17-5.00(m,2H),4.18(dd,J=12.3,5.3Hz,1H),4.09-3 .96(m,2H),3.60(ddd,J=10.1,5.3,2.4Hz,1H),2.47(s,3H),2.02(s,3H),2.01(s,3H),1.99(s ,3H),1.75(s,3H).(2R,3S,4R,5R,6S)-5-acetamido-2-(acetoxymethyl)-6-((2-(1-(((4-(trifluoromethyl)benzoyl)oxy)imino)ethyl)phenyl)thio)tetrahydro-2H-pyran-3,4-diyl diacetate

[0165] Example 3: Oxime glycosyl sulfides and their preparation method

[0166] This embodiment provides a glycosyl thioether, the preparation method of which includes the following steps:

[0167]

[0168] I. Synthesis of Compound 3

[0169] (1) Synthesis of intermediate crude products

[0170] In a round-bottom flask equipped with a magnetic stirrer, compound 1a (1.0 eq., 2.07 mmol, 1.0 g) and a catalytic amount of sodium methoxide were added. Then, 10 mL of dry methanol was added, and the flask was sealed with a rubber stopper. The mixture was stirred continuously at room temperature until compound 1a was completely consumed (TLC monitoring showed a reaction time of approximately 30 minutes). After the reaction was complete, Amberlite H+ resin was added to neutralize the reaction mixture, and the pH of the reaction solution was adjusted to 5–7. The resin was then removed by filtration, and the filtrate was collected and concentrated to obtain the crude product (the crude product did not require further purification and was used directly in the next reaction).

[0171] (2) Synthesis of compound 1i

[0172] In a round-bottom flask equipped with a magnetic stirrer, the crude product obtained in step one (1.0 eq., 2.07 mmol, 652 mg) and 10 mL of acetone were added. At room temperature, p-toluenesulfonic acid (0.4 eq., 8.30 μmol, 143 mg) and 2,2-dimethoxypropane (4.0 eq., 8.30 mmol, 1.0 mL) were added, and the flask was stoppered with a rubber stopper. Stirring continued until the sugar starter was completely consumed (TLC monitoring, reaction time approximately 6–8 hours). After the reaction was complete, saturated sodium bicarbonate aqueous solution was added to adjust the pH of the reaction mixture to 7–8. The reaction mixture was then filtered through diatomaceous earth, and the filtrate was collected and concentrated. Next, water was added to dilute the residue, and the aqueous phase was transferred to a 125 mL separatory funnel and extracted three times with 50 mL of ethyl acetate. The organic phases were combined, dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain the final product.

[0173] (3) Synthesis of compound 2i

[0174] Follow the method of step (2) in Example 1.

[0175] (4) Synthesis of compound 3i

[0176] Follow the method of step (3) in Example 1.

[0177] II. Structure and Characterization of Compounds

[0178] (1) Compound 1i

[0179] 3.74-3.68(m,2H),2.60(s,3H),1.55(s,3H),1.49(s,3H),1.40(s,3H),1.34(s,3H).

[0180] (2) Compound 2i

[0181] 5.5Hz,0.7H),3.86-3.76(m,2H),3.77-3.64(m,1H),2.27(s,2H),2.21(s,1H),1.55(s,3H),1.50(s,3H),1.44(s,3H),1.36(s,3H).

[0182] (3) Compound 3i

[0183] 3.86-3.76(m,2H),3.70(t,J=10.4Hz,1H),2.53(s,3H),1.54(s,3H),1.49( s,3H),1.38(s,3H),1.35(s,3H).1-(2-(((4R,5aR,9aR,9bS)-2,2,8,8-tetr amethylhexahydro-[1,3]dioxolo[4',5':4,5]pyrano[3,2-d][1,3]dioxin-4-yl)thio)phenyl)ethan-1-oneO-(4-(trifluoromethyl)benzoyl)oxime

[0184] Example 4: Oxime glycosyl sulfides and their preparation method

[0185] This embodiment provides a glycosyl thioether, the preparation method of which includes the following steps:

[0186]

[0187] I. Synthesis of Compound 3

[0188] (1) Synthesis of intermediate crude products

[0189] The method for synthesizing the intermediate crude product according to step (1) of Example 3.

[0190] (2) Synthesis of crude product 1d'

[0191] In a round-bottom flask equipped with a magnetic stirrer, add the crude product obtained in step one (1.0 eq., 12.10 mmol, 3.43 g) and 30 mL of acetone. At room temperature, add p-toluenesulfonic acid (0.1 eq., 1.21 mmol, 208 mg) and 2,2-dimethoxypropane (2.0 eq., 24.30 mmol, 3.0 mL), and stopper the flask with a rubber stopper. Continue stirring until the sugar starting material is completely consumed (TLC monitoring, reaction time approximately 6–8 hours). After the reaction is complete, add saturated sodium bicarbonate aqueous solution to adjust the pH of the reaction mixture to 7–8. Subsequently, filter the reaction mixture through diatomaceous earth, collect the filtrate, and concentrate it. Next, dilute the residue with 50 mL of water, transfer the aqueous phase to a 125 mL separatory funnel, and extract the aqueous phase three times with 50 mL of ethyl acetate. Combine the organic phases, dry them over anhydrous magnesium sulfate, filter, and concentrate under reduced pressure to obtain crude product 1d' (the crude product does not require further purification and can be used directly in the next reaction).

[0192] (3) Synthesis of compound 1j

[0193] In a round-bottom flask equipped with a magnetic stirrer, the crude product 1d' (1.0 eq., 12.00 mmol, 3.91 g) from step two and 4-dimethylaminopyridine (0.2 eq., 2.41 mmol, 295 mg) were added, followed by 12 mL of pyridine (reaction concentration 0.5 M). The flask was stoppered with a rubber stopper and placed in an ice-water bath to cool to 0°C. Acetic anhydride (2.0 eq., 24.10 mmol, 2.3 mL) was slowly added dropwise. After the addition was complete, the ice-water bath was removed, and stirring was continued at room temperature until the sugar starting material was completely consumed (TLC monitoring, reaction time approximately 6–10 hours). After the reaction was complete, the reaction mixture was transferred to a 250 mL separatory funnel, diluted with 100 mL of ethyl acetate, and the organic phase was washed 6 times with 100 mL of 10% citric acid aqueous solution. The organic phase was washed with 100 mL of saturated saline solution and separated. It was dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain the final product.

[0194] (4) Synthesis of compound 2j

[0195] Follow the method of step (2) in Example 1.

[0196] (5) Synthesis of compound 3j

[0197] Follow the method of step (3) in Example 1.

[0198] II. Structure and Characterization of Compounds

[0199] (1) Compound 1j

[0200] = 11.6, 6.4 Hz, 1H), 4.18 (dd, J = 11.6, 5.4 Hz, 1H), 2.60 (s, 3H), 2.07 (s, 3H), 1.54 (s, 3H), 1.36 (s, 3H).

[0201] β configuration: 1 1H NMR (CDCl3, 400 MHz) δ: 7.72 (dd, J = 8.1, 1.2 Hz, 1H), 7.65 (dd, J = 7.8, 1.6 Hz, 1H), 7.40 (td, J = 7.6, 1.5 Hz, 1H), 7.24 (td, J = 7.5, 1.3 Hz, 1H), 5.47 (d, J = 4.6 Hz, 1H), 4.97 (dd, J = 6.4, 4.6 Hz, 1H), 4.66 (dd, J = 6.4, 2.6 Hz, 1H), 4.43 (td, J = 4.8, 2.5 Hz, 1H), 4.25 (dd, J = 11.9, 5.1 Hz, 1H), 4.17 (dd, J = 12.0, 4.3 Hz, 1H), 2.57 (s, 3H), 2.06 (s, 3H), 1.60 (s, 3H), 1.35 (s, 3H).

[0202] (2) Compound 2j

[0203] 2.0 Hz, 1H), 4.72 (dd, J = 6.2, 1.8 Hz, 1H), 4.44 - 4.36 (m, 1H), 4.39 - 4.30 (m, 1H), 4.20 (dd, J = 11.3, 5.3 Hz, 1H), 2.23 (s, 2.7H), 2.18 (s, 0.3H), 2.10 (s, 0.3H), 2.08 (s, 2.7H), 1.51 (s, 2.7H), 1.49 (s, 0.3H), 1.34 (s, 2.7H), 1.33 (s, 0.3H).

[0204] (3) Compound 3j

[0205] 1H), 2.51 (s, 3H), 2.07 (s, 3H), 1.49 (s, 3H), 1.32 (s, 3H). ((3aR, 4R, 6R, 6aR)-2,2-dimethyl-6-((2-(1-(((4-(trifluoromethyl)benzoyl)oxy)imino)ethyl)phenyl)thio)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl acetate

[0206] Example 5: Oxime-based glycosyl sulfides and their preparation method

[0207] This embodiment provides a glycosyl thioether, the preparation method of which includes the following steps:

[0208]

[0209] I. Synthesis of Compound 3

[0210] (1) Synthesis of compound 1k'

[0211] In a round-bottom flask equipped with a magnetic stirrer, add 1.0 eq. (10.00 mmol, 2.6 g) of fully acetyl-protected starting sugar. In a glove box (nitrogen atmosphere), add 20 mL of dry dichloromethane (0.5 M reaction concentration) and stopper with a rubber stopper. Place the flask in an ice-water bath and cool to 0°C. Insert a nitrogen balloon and slowly add 1.5 mL of 2-mercaptoacetophenone (1.5 eq., 15.00 mmol, 2.28 g). After stirring for 10 minutes, slowly add 1.2 eq. (12.00 mmol, 1.5 mL) of boron trifluoride ether. After the addition is complete, remove the ice-water bath and continue stirring at room temperature until the sugar starting sugar is completely consumed (TLC monitoring, reaction time approximately 1–2 hours). After the reaction is complete, place the flask in an ice-water bath and cool to 0°C. Slowly add 3.3 mL of triethylamine to quench any excess boron trifluoride ether. Next, the mixture was concentrated under reduced pressure, and the residue was separated and purified by column chromatography to obtain the final product.

[0212] (2) Synthesis of intermediate crude products

[0213] Follow the method of step (1) in Example 3.

[0214] (3) Synthesis of compound 1k

[0215] In a round-bottom flask equipped with a magnetic stirrer, add the crude product obtained in step one (1.0 eq., 8.85 mmol, 2.38 g) and 30 mL of acetone. At room temperature, add p-toluenesulfonic acid (0.1 eq., 8.85 μmol, 153 mg) and 2,2-dimethoxypropane (2.0 eq., 17.80 mmol, 2.2 mL), and stopper the flask. Continue stirring until the sugar starter is completely consumed (TLC monitoring, reaction time approximately 6–8 hours). After the reaction is complete, add saturated sodium bicarbonate aqueous solution to adjust the pH of the reaction mixture to 7–8. Subsequently, filter the reaction mixture through diatomaceous earth, collect the filtrate, and concentrate it. Next, dilute the residue with 50 mL of water, transfer the aqueous phase to a 125 mL separatory funnel, and extract the aqueous phase three times with 50 mL of ethyl acetate. Combine the organic phases, dry over anhydrous magnesium sulfate, filter, concentrate under reduced pressure, and purify the residue by column chromatography to obtain the final product.

[0216] (4) Synthesis of compound 2k

[0217] Follow the method of step (2) in Example 1.

[0218] (5) Synthesis of compound 3k

[0219] Follow the method of step (3) in Example 1.

[0220] II. Structure and Characterization of Compounds

[0221] (1) Compound 1k'

[0222] 5.33(t,J=5.5Hz,0.8H),5.13(t,J=4.9Hz,0.8H),4.89(t,J=6.4Hz,0.2H),4.35(p,J=6.4Hz,0.2H),4.25(qd,J=6.5,4.6Hz,0.8H),2.61( s,2.4H),2.60(s,0.6H),2.16(s,0.6H),2.12(s,0.6H),2.08(s,2.4H),2.08(s,2.4H),1.38(d,J=6.5Hz,2.4H),1.37(d,J=6.2Hz,0.6H).

[0223] (2) Compound 1k

[0224] 8.1Hz,1H),7.62(dd,J=7.8,1.6Hz,1H),7.39(td,J=7.6,1.6Hz,1H),7.22(td,J=7.5,1.3Hz,1H),5.43(d,J=4.9Hz,1H),4.96(dd,J=6 .6,4.8Hz,1H),4.39(dd,J=6.5,3.3Hz,1H),4.33(qd,J=6.6,3.2Hz,1H),2.57(s,3H),1.59(s,3H),1.33(s,3H),1.25(d,J=6.6Hz,3H).

[0225] (3) Compound 2k

[0226] 2.7H), 1.49 (s, 0.3H), 1.40 (d, J = 7.0Hz, 3H), 1.33 (s, 2.7H), 1.31 (s, 0.3H).

[0227] (4) Compound 3k

[0228] 1-(2-(((3aR,4R,6R,6aR)-2,2,6-trimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)thio)phenyl)ethan-1-one O-(4-(trifluoromethyl)benzoyl)oxime

[0229] Example 6: Oxime glycosyl sulfides and their preparation method

[0230] This embodiment provides a glycosyl thioether, the preparation method of which includes the following steps:

[0231]

[0232] I. Synthesis of Compound 3

[0233] (1) Synthesis of intermediate crude products

[0234] Follow the method of step (1) in Example 3.

[0235] (2) Synthesis of compound 1l

[0236] In a round-bottom flask equipped with a magnetic stirrer, add the crude product obtained in step one (1.0 eq., 2.10 mmol, 650 mg) and 20 mL of dry dichloromethane. At room temperature, add imidazole (1.2 eq., 2.50 mmol, 170 mg) and tert-butyldiphenylchlorosilane (1.2 eq., 2.50 mmol, 650 μL, abbreviated as TBDPS), and stopper the flask. Continue stirring until the sugar starting material is completely consumed (TLC monitoring, reaction time approximately 6–8 hours). After the reaction is complete, transfer the reaction solution to a 250 mL separatory funnel and dilute with 100 mL of ethyl acetate. After washing the organic phase three times with 100 mL of water, separate the solution, dry it over anhydrous magnesium sulfate, filter, concentrate under reduced pressure, and purify the residue by column chromatography to obtain the final product.

[0237] (3) Synthesis of compound 2l

[0238] Follow the method of step (2) in Example 1.

[0239] (4) Synthesis of compound 3l

[0240] The method is the same as in step (3) of Example 1, except that the amount of compound 2 is 1.0 eq., 2.70 mmol, 1.5 g; triethylamine is replaced with pyridine, the amount of pyridine is 1.1 eq., 3.00 mmol, 240 μL; and the amount of trifluoromethylbenzoyl chloride is 1.1 eq., 3.00 mmol, 442 μL.

[0241] II. Structure and Characterization of Compounds

[0242] (1) Compound 1l

[0243]

[0244] (2) Compound 2l

[0245] J=9.5Hz,1H),2.13(s,3H),1.01(s,9H).

[0246] (2) Compound 3l

[0247] 1.8Hz,1H),5.59(d,J=1.5Hz,1H),4.21-4.14(m,2H),3.97(dd,J=10.8,4. 4Hz,1H),3.90(dd,J=10.8,5.4Hz,1H),3.85(t,J=9.3Hz,1H),3.76(dd,J=9 .3,3.4Hz,1H),3.33(s,3H),2.47(s,3H),1.05(s,9H).1-(2-(((2R,3S,4S,5S,6R)-6-(((tert-butyldiphenylsilyl)oxy)methyl)-3,4,5-trihydrox ytetrahydro-2H-pyran-2-yl)thio)phenyl)ethan-1-one O-(4-(trifluoromethyl)benzoyl)oxime

[0248] Example 7 Oxime glycosyl sulfides and their preparation method

[0249] This embodiment provides a glycosyl thioether, the preparation method of which includes the following steps:

[0250]

[0251] I. Synthesis of Compound 3

[0252] (1) Synthesis of crude product 1m'

[0253] In a round-bottom flask equipped with a magnetic stirrer, add 1-hydroxydiketide furanomannose (1.0 eq., 96.00 mmol, 25 g) and 4-dimethylaminopyridine (0.1 eq., 9.60 mmol, 1.17 g), followed by 50 mL of pyridine (reaction concentration 2 M). Stopper the flask with a rubber stopper and place it in an ice-water bath to cool to 0°C. Slowly add acetic anhydride (2.0 eq., 192.00 mmol, 18 mL). After the addition is complete, remove the ice-water bath and continue stirring at room temperature until the sugar starting material is completely consumed (TLC monitoring, reaction time approximately 3–5 hours). After the reaction is complete, transfer the reaction mixture to a 500 mL separatory funnel, dilute with 250 mL of ethyl acetate, and wash the organic phase six times with 250 mL of 10% citric acid aqueous solution. The organic phase was washed with 250 mL of saturated brine and separated. It was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to obtain crude product 1m' (the crude product does not need to be separated and purified, and can be used directly in the next reaction).

[0254] (2) Synthesis of crude product 1m”

[0255] In a round-bottom flask equipped with a magnetic stirrer, add the crude product 1m' (1.0 eq., 10.00 mmol, 3.0 g) from step one. In a glove box (nitrogen atmosphere), add 20 mL of dry dichloromethane (reaction concentration 0.5 M) and stopper with a rubber stopper. Place the flask in an ice-water bath and cool to 0°C. Slowly add trimethylbromosilane (2.0 eq., 20.00 mmol, 2.6 mL). After the addition is complete, remove the ice-water bath and continue stirring at room temperature until the sugar starting material is completely consumed (TLC monitoring, reaction time approximately 5–8 hours). After the reaction is complete, distill under reduced pressure (water bath temperature <30°C during distillation) to obtain the crude product 1m (the crude product does not require separation and purification and can be used directly in the next reaction).

[0256] (3) Synthesis of compound 1m

[0257] In a round-bottom flask equipped with a magnetic stirrer, add 0.8 eq. (8.00 mmol, 1.22 g) of 2-mercaptoacetone and 10 mL of dry acetonitrile. At room temperature, add triethylamine (1.5 eq., 15.00 mmol, 2.1 mL) and stopper with a rubber stopper. After stirring for 30 minutes, place the flask in an ice-water bath to cool to 0°C, and slowly add 10 mL of a dry acetonitrile solution of bromosaccharide (1.0 eq., 10.00 mmol, 3.23 g). After the addition is complete, remove the ice-water bath and continue stirring at room temperature until the sugar starting material is completely consumed (TLC monitoring, reaction time approximately 5–8 hours). After the reaction is complete, transfer the reaction mixture to a 250 mL separatory funnel, dilute with 100 mL of ethyl acetate, and wash the organic phase three times with 100 mL of water. The organic phase was washed with 100 mL of saturated saline solution and separated. It was dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain the final product.

[0258] (4) Synthesis of compound 2m

[0259] Follow the method of step (2) in Example 1.

[0260] (5) Synthesis of compound 3m

[0261] Follow the method of step (3) in Example 1.

[0262] II. Structure and Characterization of Compounds

[0263] (1) Compound 1m

[0264]

[0265] (2) Compound 2m

[0266] 1.45(s,3H),1.39(s,3H),1.36(s,3H).

[0267] (3) Compound 3m

[0268] 7.8,5.6,4.6Hz,1H),4.17-4.07(m,2H),3.55(dd,J=7.8,3.5Hz,1H),2.54 (s,3H),1.55(s,3H),1.42(s,3H),1.37(s,3H),1.35(s,3H).1-(2-(((3aS ,4S,6R,6aS)-6-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)thio)phenyl)ethan-1-one O-(4-(trifluoromethyl)benzoyl)oxime

[0269] Example 8: Application of oxime glycosyl thioethers in the synthesis of C-glycosides

[0270] In this embodiment, a series of visible-light-catalyzed β-carbonyl-α-alkyl C-glycosides were synthesized using glycosyl thioethers as glycosyl radical donors and styrene compounds as glycosyl acceptors. The synthetic method includes the following steps:

[0271]

[0272] I. Synthesis of Compound 4

[0273] In an 8 mL screw-top reaction flask equipped with a magnetic stir bar and a dryer, glycosyl donor 3 (1.0 eq., 0.15 mmol), olefinic glycosyl acceptor (3.0 eq., 0.45 mmol), and Ir(ppy)3 (0.02 eq., 3.00 μmol) were added. Under a nitrogen atmosphere in a glove box, 3 mL of dry dimethyl sulfoxide was added to the flask using a 5 mL syringe, and the cap was tightened. The reaction mixture was continuously stirred at room temperature under 455 nm LED irradiation until the glycosyl donor was completely consumed (reaction time: 6 hours). After the reaction, the reaction mixture was transferred to a 250 mL separatory funnel and diluted with 100 mL of ethyl acetate. The organic phase was washed twice with 100 mL of saturated sodium bicarbonate aqueous solution and 100 mL of water, respectively, and then dried over anhydrous magnesium sulfate. The mixture was filtered, concentrated under reduced pressure, and the residue was purified by column chromatography to obtain the final product.

[0274] II. Structure and Characterization of Compounds

[0275] (1) Compound 4a

[0276] (dt, J = 8.4, 5.0 Hz, 1H), 4.41 (dd, J = 12.0, 6.8 Hz, 1H), 4.17 (dd, J = 12.0, 3.8 Hz, 1H), 4.01 (td, J = 6.6, 3.8 Hz, 1H), 3.43 (dd, J = 16.1, 8.4 Hz, 1H), 3.18 (dd, J = 16.1, 4.9 Hz, 1H), 2.08 (s, 3H), 2.074 (s, 3H), 2.066 (s, 3H), 2.03 (s, 3H). (2R,3R,4R,5R,6R)-2-(2-([1,1'-biphenyl]-4-yl)-2-oxoethyl)-6-(acetoxymethyl)tetrahydro-2H-pyran-3,4,5-triyltriacetate

[0277] (2) Compound 4b

[0278]

[0279] = 12.0, 3.9 Hz, 1H), 3.98 (td, J = 6.6, 3.9 Hz, 1H), 3.39 (dd, J = 16.1, 8.4 Hz, 1H), 3.15 (dd, J = 16.1, 4.9 Hz, 1H), 2.07 (s, 3H), 2.059 (s, 3H), 2.056 (s, 3H), 2.03 (s, 3H).

[0280] (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-oxo-2-phenylethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0281] (3) Compound 4c

[0282] 3.9 Hz, 1H), 3.98 (td, J = 6.6, 3.8 Hz, 1H), 3.36 (dd, J = 16.1, 8.4 Hz, 1H), 3.12 (dd, J = 16.1, 5.0 Hz, 1H), 2.40 (s, 3H), 2.08 (s, 3H), 2.06 (s, 3H), 2.05 (s, 3H), 2.03 (s, 3H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-oxo-2-(p-tolyl)ethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0283] (4) Compound 4d

[0284] The yield was 58%. Structural characterization data are as follows: 1 H NMR (CDCl3)

[0285] =12.0,,6.7Hz,1H),4.15(dd,J=12.0,3.9Hz,1H),3.98(td,J=6.6,3.9Hz,1H),3 .38(dd,J=16.2,8.4Hz,1H),3.15(dd,J=16.2,5.0Hz,1H),2.08(s,3H),2.07(s, 3H),2.06(s,3H),2.04(s,3H).(2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-(hydroxymethyl)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0286] (5) Compound 4e

[0287] 8.2Hz,1H),4.61(ddd,J=7.6,6.4,3.5Hz,1H),4.27(dd,J=12.1,6.1Hz,1H),4.09(dd, J=12.1,3.3Hz,1H),3.95(ddd,J=7.9,6.1,3.2Hz,1H),3.91(s,3H),3.42-3.32(m,2H), 2.08(s,3H),2.045(s,3H),2.039(s,3H),2.01(s,3H).(2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(2-methoxyphenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0288] (6) Compound 4f

[0289] 5.0 Hz, 1H), 4.38 (dd, J = 12.0, 6.7 Hz, 1H), 4.15 (dd, J = 12.0, 3.9 Hz, 1H), 3.97 (td, J = 6.6, 3.9 Hz, 1H), 3.83 (s, 3H), 3.37 (dd, J = 16.2, 8.3 Hz, 1H), 3.13 (dd, J = 16.2, 5.0 Hz, 1H), 2.07 (s, 3H), 2.06 (s, 3H), 2.05 (s, 3H), 2.03 (s, 3H). (2R, 3R, 4R, 5R, 6R)-2-(acetoxymethyl)-6-(2-(3-methoxyphenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0290] (7) Compound 4g

[0291] = 12.0, 3.8 Hz, 1H), 3.97 (td, J = 6.6, 3.8 Hz, 1H), 3.85 (s, 3H), 3.33 (dd, J = 16.0, 8.3 Hz, 1H), 3.09 (dd, J = 16.0, 5.1 Hz, 1H), 2.06 (s, 3H), 2.05 (s, 3H), 2.04 (s, 3H), 2.02 (s, 3H). (2R, 3R, 4R, 5R, 6R)-2-(acetoxymethyl)-6-(2-(4-methoxyphenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0292] (8) Compound 4h

[0293] Hz, 1H), 4.65 (dt, J = 8.3, 5.0 Hz, 1H), 4.59 (dt, J = 5.3, 1.5 Hz, 2H), 4.37 (dd, J = 12.0, 6.7 Hz, 1H), 4.15 (dd, J = 12.0, 3.9 Hz, 1H), 3.97 (td, J = 6.6, 3.8 Hz, 1H), 3.33 (dd, J = 16.0, 8.3 Hz, 1H), 3.09 (dd, J = 16.0, 5.1 Hz, 1H), 2.06 (s, 3H), 2.05 (s, 3H), 2.04 (s, 3H), 2.02 (s, 3H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-(allyloxy)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0294] (9) Compound 4i

[0295] 4.68 (dt, J = 8.3, 5.1 Hz, 1H), 4.40 (dd, J = 12.0, 6.7 Hz, 1H), 4.17 (dd, J = 12.0, 3.9 Hz, 1H), 3.99 (td, J = 6.6, 3.9 Hz, 1H), 3.35 (dd, J = 16.0, 8.4 Hz, 1H), 3.12 (dd, J = 16.0, 5.0 Hz, 1H), 2.09 (s, 3H), 2.08 (s, 3H), 2.07 (s, 3H), 2.05 (s, 3H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-oxo-2-(4-phenoxyphenyl)ethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0296] (10) Compound 4j

[0297] 4.179 (dd, J = 12.0, 4.0 Hz, 1H), 3.99 (td, J = 6.5, 4.0 Hz, 1H), 3.38 (dd, J = 16.1, 8.5 Hz, 1H), 3.11 (dd, J = 16.1, 4.7 Hz, 1H), 2.33 (s, 3H), 2.10 (s, 3H), 2.08 (s, 3H), 2.08 (s, 3H), 2.05 (s, 3H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-acetoxyphenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0298] (11) Compound 4k

[0299] 4.13 (dd, J = 12.0, 3.8 Hz, 1H), 3.96 (td, J = 6.6, 3.8 Hz, 1H), 3.34 (dd, J = 16.2, 8.1 Hz, 1H), 3.11 (dd, J = 16.2, 5.2 Hz, 1H), 2.17 (s, 3H), 2.06 (s, 6H), 2.03 (s, 3H), 2.02 (s, 3H). (2R,3R,4R,5R,6R)-2-(2-(4-acetamidophenyl)-2-oxoethyl)-6-(acetoxymethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0300] (12) Compound 4l

[0301]

[0302] (dd, J = 12.0, 6.5 Hz, 1H), 4.16 (dd, J = 12.0, 3.9 Hz, 1H), 3.98 (td, J = 6.4, 4.0 Hz, 1H), 3.35 (dd, J = 16.1, 8.8 Hz, 1H), 3.17 (dd, J = 16.1, 4.7 Hz, 1H), 2.41 (s, 3H), 2.064 (s, 3H), 2.056 (s, 3H), 2.05 (s, 6H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(2-(methylthio)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0303] (13) Compound 4m

[0304] 3.3 Hz, 1H), 5.12 (t, J = 6.6 Hz, 1H), 4.67 (dt, J = 8.5, 5.1 Hz, 1H), 4.43 (dd, J = 12.0, 6.9 Hz, 1H), 4.17 (dd, J = 12.1, 4.0 Hz, 1H), 3.99 (td, J = 6.5, 4.0 Hz, 1H), 3.36 (dd, J = 16.1, 8.4 Hz, 1H), 3.12 (dd, J = 16.1, 4.8 Hz, 1H), 2.10 (s, 3H), 2.08 (s, 6H), 2.05 (s, 3H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-fluorophenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0305] (14) Compound 4n

[0306] 16.2, 8.4 Hz, 1H), 3.10 (dd, J = 16.2, 4.8 Hz, 1H), 2.07 (s, 3H), 2.06 (s, 6H), 2.02 (s, 3H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-chlorophenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0307] (15) Compound 4o

[0308] 4.0 Hz, 1H), 3.98 (td, J = 6.5, 4.1 Hz, 1H), 3.34 (dd, J = 16.2, 8.5 Hz, 1H), 3.10 (dd, J = 16.1, 4.7 Hz, 1H), 2.09 (s, 3H), 2.074 (s, 3H), 2.069 (s, 3H), 2.04 (s, 3H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-bromophenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0309] (16) Compound 4p

[0310] 1H), 4.43 (dd, J = 12.0, 6.9 Hz, 1H), 4.16 (dd, J = 12.1, 4.0 Hz, 1H), 3.98 (td, J = 6.5, 4.1 Hz, 1H), 3.95 (s, 3H), 3.42 (dd, J = 16.4, 8.3 Hz, 1H), 3.18 (dd, J = 16.4, 4.8 Hz, 1H), 2.08 (s, 3H), 2.07 (s, 3H), 2.07 (s, 3H), 2.04 (s, 3H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(3-(methoxycarbonyl)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyltriacetate

[0311] (17) Compound 4q

[0312] At 400 MHz) δ: 7.92 - 7.88 (m, 4H), 5.31 (dd, J = 7.3, 3.3 Hz, 1H), 5.24 (dd, J = 5.3, 3.3 Hz, 1H), 5.12 (t, J = 6.7 Hz, 1H), 4.68 (dt, J = 8.5, 5.0 Hz, 1H), 4.40 (dd, J = 12.0, 6.9 Hz, 1H), 4.15 (dd, J = 12.0, 3.9 Hz, 1H), 3.98 (td, J = 6.6, 3.9 Hz, 1H), 3.41 (dd, J = 16.2, 8.4 Hz, 1H), 3.14 (dd, J = 16.2, 4.8 Hz, 1H), 2.09 (s, 3H), 2.07 (s, 6H), 2.04 (s, 3H), 1.35 (s, 12H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-oxo-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0313] (18) Compound 4r

[0314] J=12.0,4.1Hz,1H),4.04-3.96(m,1H),3.42(dd,J=16.3,8.5Hz,1H),3.18(dd,J=16.3,4.6Hz,1H),2.10(s,3H),2.09(s,3H),2.08(s,3 H),2.06(s,3H).(2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-formylphenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0315] (19) Compound 4s

[0316] The yield was 67%. Structural characterization data are as follows: 1 H NMR (CDCl3, 400)

[0317] =12.0,7.1Hz,1H),4.17(dd,J=12.0,4.1Hz,1H),3.99(dt,J=6.9,4.6Hz,1H), 3.32(dd,J=16.2,8.5Hz,1H),3.08(dd,J=16.1,4.6Hz,1H),2.10(s,3H),2.09( s,3H),2.08(s,3H),2.06(s,3H).(2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(3,4-difluorophenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0318] (20) Compound 4t

[0319] The yield was 90%. Structural characterization data are as follows: 1 H NMR (CDCl3,

[0320] =7.3, 6.1 Hz, 1H), 4.67 (dt, J=8.3, 5.0 Hz, 1H), 4.41 (dd, J=12.0, 6.8 Hz, 1H), 4.15 (dd, J=12.0, 3.9 Hz, 1H), 3.98 (td, J=6.5, 4.0 Hz, 1H), 3.39 (dd, J=16.2, 8.3 Hz, 1H), 3.14 (dd, J=16.1, 4.9 Hz, 1H), 2.07 (s, 3H), 2.06 (s, 3H), 2.05 (s, 3H), 2.02 (s, 3H). (2R,3R,4R,5R,6R)-2-(2-(4-(1H-pyrazol-1-yl)phenyl)-2-oxoethyl)-6-(acetoxymethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0321] (21) Compound 4u

[0322] MHz) δ: 8.67 (s, 1H), 8.12 (s, 1H), 8.08 (d, J=8.8 Hz, 2H), 7.82 (d, J=8.7 Hz, 2H), 5.31 (dd, J=7.1, 3.3 Hz, 1H), 5.23 (dd, J=5.6, 3.3 Hz, 1H), 5.10 (t, J=6.5 Hz, 1H), 4.66 (dt, J=8.4, 5.1 Hz, 1H), 4.43 (dd, J=12.0, 6.9 Hz, 1H), 4.15 (dd, J=12.1, 4.1 Hz, 1H), 3.99 (td, J=6.5, 4.2 Hz, 1H), 3.39 (dd, J=16.2, 8.4 Hz, 1H), 3.16 (dd, J=16.2, 4.8 Hz, 1H), 2.07 (s, 3H), 2.06 (s, 6H), 2.03 (s, 3H). (2R,3R,4R,5R,6R)-2-(2-(4-(1H-1,2,4-triazol-1-yl)phenyl)-2-oxoethyl)-6-(acetoxymethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0323] (22) Compound 4v

[0324] 1H), 4.36 (dd, J = 12.1, 6.6 Hz, 1H), 4.14 (dd, J = 12.1, 3.7 Hz, 1H), 4.01 (td, J = 6.6, 3.7 Hz, 1H), 3.50 (dd, J = 15.7, 9.5 Hz, 1H), 3.27 (dd, J = 15.7, 4.3 Hz, 1H), 2.09 (s, 3H), 2.08 (s, 3H), 2.07 (s, 3H), 2.01 (s, 3H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(naphthalen-1-yl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0325] (23) Compound 4w

[0326] (dd, J = 5.2, 3.4 Hz, 1H), 5.15 (t, J = 6.8 Hz, 1H), 4.76 (dt, J = 9.1, 5.0 Hz, 1H), 4.43 (dd, J = 12.0, 6.8 Hz, 1H), 4.18 (dd, J = 12.0, 3.9 Hz, 1H), 4.03 (td, J = 6.6, 3.9 Hz, 1H), 3.55 (dd, J = 16.1, 8.4 Hz, 1H), 3.27 (dd, J = 16.1, 4.8 Hz, 1H), 2.10 (s, 3H), 2.08 (s, 6H), 2.02 (s, 3H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(naphthalen-2-yl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0327] (24) Compound 4x

[0328] 1H), 4.70 (dt, J = 8.3, 5.0 Hz, 1H), 4.39 (dd, J = 12.0, 6.7 Hz, 1H), 4.16 (dd, J = 12.0, 3.9 Hz, 1H), 3.99 (td, J = 6.6, 3.9 Hz, 1H), 3.45 (dd, J = 16.1, 8.4 Hz, 1H), 3.20 (dd, J = 16.1, 5.0 Hz, 1H), 2.07 (s, 3H), 2.06 (s, 3H), 2.05 (s, 3H), 2.01 (s, 3H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(benzofuran-5-yl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0329] (25) Compound 4y

[0330] 2H), 4.39 (dd, J = 12.1, 6.5 Hz, 1H), 4.15 (dd, J = 12.1, 3.8 Hz, 1H), 3.97 (td, J = 6.6, 3.8 Hz, 1H), 3.51 (td, J = 8.7, 3.6 Hz, 2H), 3.36 (dd, J = 16.2, 8.3 Hz, 1H), 3.15 (dd, J = 16.2, 5.0 Hz, 1H), 2.08 (s, 3H), 2.07 (s, 3H), 2.052 (s, 3H), 2.048 (s, 3H).

[0331] (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(2,3-dihydrobenzofuran-5-yl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0332] (26) Compound 4z

[0333] 8.7, 5.1 Hz, 1H), 4.41 (dd, J = 12.0, 6.9 Hz, 1H), 4.16 (dd, J = 12.0, 4.0 Hz, 1H), 4.00 (td, J = 6.5, 4.0 Hz, 1H), 3.20 (dd, J = 15.5, 8.5 Hz, 1H), 2.97 (dd, J = 15.5, 4.8 Hz, 1H), 2.08 (s, 3H), 2.06 (s, 6H), 2.01 (s, 3H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-oxo-2-(1-phenyl-1H-pyrazol-4-yl)ethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0334] (27) Compound 4aa

[0335] 4.15 (dd, J = 12.0, 4.0 Hz, 1H), 4.00 (td, J = 6.6, 4.1 Hz, 1H), 3.30 (dd, J = 15.5, 8.8 Hz, 1H), 3.05 (dd, J = 15.5, 4.7 Hz, 1H), 2.08 (s, 3H), 2.06 (s, 3H), 2.04 (s, 3H), 2.01 (s, 3H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-oxo-2-(thiophen-2-yl)ethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0336] (28) Compound 4ab

[0337] Hz, 1H), 4.43 (dd, J = 12.0, 7.2 Hz, 1H), 4.15 (dd, J = 12.0, 3.9 Hz, 1H), 4.03 (td, J = 6.7, 4.1 Hz, 1H), 3.40 (dd, J = 15.5, 8.7 Hz, 1H), 3.14 (dd, J = 15.5, 4.8 Hz, 1H), 2.09 (s, 3H), 2.08 (s, 3H), 2.06 (s, 3H), 1.94 (s, 3H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(benzo[b]thiophen-3-yl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0338] (29) Compound 4ac

[0339] 12.0, 7.0 Hz, 1H), 4.13 (dd, J = 12.0, 4.0 Hz, 1H), 4.00 - 3.93 (m, 4H), 3.30 (dd, J = 15.9, 8.5 Hz, 1H), 3.06 (dd, J = 15.9, 4.7 Hz, 1H), 2.07 (s, 3H), 2.05 (s, 6H), 2.01 (s, 3H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(6-methoxypyridin-3-yl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0340] (30) Compound 4ad

[0341] 12.0, 7.1 Hz, 1H), 4.13 (dd, J = 12.0, 4.0 Hz, 1H), 4.02 - 3.93 (m, 1H), 3.34 (dd, J = 16.1, 8.5 Hz, 1H), 3.10 (dd, J = 16.0, 4.6 Hz, 1H), 2.61 (s, 3H), 2.08 (s, 3H), 2.062 (s, 3H), 2.055 (s, 3H), 2.02 (s, 3H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(6-methylpyridin-3-yl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0342] (31) Compound 4ae

[0343]

[0344] 6.1 Hz, 1H), 4.09 (dd, J = 12.1, 3.4 Hz, 1H), 4.04 (s, 3H), 3.95 (ddd, J = 7.6, 6.2, 3.4 Hz, 1H), 3.44 - 3.29 (m, 2H), 2.08 (s, 3H), 2.046 (s, 3H), 2.043 (s, 3H), 2.02 (s, 3H).

[0345] (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(2-methoxypyridin-3-yl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0346] (32) Compound 4af

[0347] 2.40 (dd, J=16.0, 4.9 Hz, 1H), 2.06 (s, 3H), 2.06 (s, 6H), 2.02 (s, 3H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-oxo-4,4-diphenylbut-3-en-1-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0348] (33) Compound 4ag

[0349] J=6.5, 3.9 Hz, 1H), 3.31 (dd, J=16.3, 8.1 Hz, 1H), 3.09 (dd, J=16.3, 5.1 Hz, 1H), 2.08 (s, 3H), 2.07 (s, 3H), 2.06 (s, 3H), 2.05 (s, 3H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(4-(1,2,2-triphenylvinyl)phenyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0350] (34) Compound 4ah

[0351] 6.7 Hz, 1H), 4.13 (dd, J = 12.0, 3.9 Hz, 1H), 3.96 (td, J = 6.5, 3.9 Hz, 1H), 3.69 (s, 3H), 3.34 (dd, J = 16.2, 8.4 Hz, 1H), 3.17 (dd, J = 13.8, 5.8 Hz, 1H), 3.14 - 3.03 (m, 2H), 2.06 (s, 3H), 2.044 (s, 3H), 2.039 (s, 3H), 2.02 (s, 3H), 1.38 (s, 9H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-((S)-2-((tert-butoxycarbonyl)oxy)-3-methoxy-3-oxopropyl)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0352] (35) Compound 4ai

[0353] (t, J = 7.0 Hz, 1H), 4.66 (dt, J = 8.3, 5.1 Hz, 1H), 4.48 (tt, J = 10.4, 5.3 Hz, 3H), 4.39 (dd, J = 12.1, 6.7 Hz, 1H), 4.30 - 4.20 (m, 1H), 4.15 (dd, J = 12.0, 3.8 Hz, 1H), 3.98 (td, J = 6.6, 3.8 Hz, 1H), 3.65 - 3.51 (m, 1H), 3.51 - 3.42 (m, 1H), 3.35 (dd, J = 16.2, 8.2 Hz, 1H), 3.10 (dd, J = 16.2, 5.0 Hz, 1H), 2.45 (s, 1H), 2.07 (s, 6H), 2.05 (s, 3H), 2.03 (s, 3H), 2.00 - 1.85 (m, 3H). (2R,3R,4R,5R,6R)-2-(2-(4-((S)-1-(((9H-fluoren-9-yl)methoxy)carbonyl)pyrrolidine-2-carboxamido)phenyl)-2-oxoethyl)-6-(acetoxymethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0354] (36) Compound 4aj

[0355] (CDCl3,400MHz)δ:1H NMR (CDCl3, 400MHz) δ: 8.72 (s, 1H), 7.86 (t, J = 8.8Hz, 2H), 7.57 (dd, J = 11.0, 8.5Hz, 2H), 7.46- 7.39(m,6H),7.27(td,J=8.3,7.7,2.5Hz,6H),7.24-7.18(m,3H),5.33(dd,J=7.5,3.3Hz,1H), 5.26(dd,J=5.1,3.3Hz,1H),5.15(t,J=6.9Hz,1H),5.03(dd,J=15.7,7.5Hz,1H),4.67(dt,J=8 .0,5.1Hz,1H),4.41(dd,J=12.1,6.7Hz,1H),4.16(dd,J=12.0,3.8Hz,1H),3.99(td,J=6.6,3.8 Hz,2H),3.35(dd,J=16.1,8.2Hz,1H),3.11(dd,J=16.2,5.0Hz,1H),2.74(dd,J=13.1,7.1Hz,1 H),2.67(dd,J=13.1,5.5Hz,1H),2.08(s,3H),2.07(s,3H),2.06(s,3H),2.03(s,3H),1.42(s, 9H).(2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-((R)-2-((tert-butoxycarbonyl)amino)-3-(tritylthio)propanamido)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0356] Example 9: Application of glycosyl thioethers in the synthesis of C-glycosides

[0357] In this embodiment, a series of visible-photocatalyzed β-carbonyl-α-alkyl C-glycosides were synthesized using glycosyl thioethers as glycosyl radical donors and styryl drugs as glycosyl acceptors. The synthetic method includes the following steps:

[0358]

[0359] I. Synthesis of Compound 5

[0360] The method is the same as in Example 8, except that the olefin glycosyl receptor is replaced with a styrene-based drug, and the amount of the styrene-based drug is 2.0 eq., 0.30 mmol.

[0361] II. Structure and Characterization of Compounds

[0362] (1) Compound 5a

[0363] 3.4 Hz, 1H), 5.14 (t, J = 6.8 Hz, 1H), 4.97 (d, J = 13.3 Hz, 1H), 4.90 (d, J = 13.3 Hz, 1H), 4.67 (dt, J = 9.6, 5.0 Hz, 1H), 4.42 (dd, J = 12.1, 6.7 Hz, 1H), 4.18 (dd, J = 12.0, 3.9 Hz, 1H), 3.99 (td, J = 6.5, 4.0 Hz, 1H), 3.48 (s, 3H), 3.36 (dd, J = 16.2, 8.4 Hz, 1H), 3.13 (dd, J = 16.2, 4.8 Hz, 1H), 2.33 (s, 6H), 2.09 (s, 3H), 2.08 (s, 6H), 2.05 (s, 3H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-((((S)-2-((4,6-dimethylpyrimidin-2-yl)oxy)-3-methoxy-3,3-diphenylpropanoyl)oxy)methyl)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0364] (2) Compound 5b

[0365] = 8.4 Hz, 2H), 7.62 (d, J = 8.2 Hz, 2H), 7.35 (d, J = 8.1 Hz, 2H), 7.16 (d, J = 8.0 Hz, 2H), 6.93 (d, J = 8.0 Hz, 2H), 6.23 (t, J = 5.8 Hz, 1H), 5.31 (dd, J = 7.4, 3.3 Hz, 1H), 5.25 (dd, J = 5.1, 3.4 Hz, 1H), 5.13 (t, J = 6.9 Hz, 1H), 4.67 (dt, J = 9.3, 5.3 Hz, 1H), 4.40 (dd, J = 12.0, 6.7 Hz, 1H), 4.15 (dd, J = 12.0, 3.9 Hz, 1H), 3.98 (td, J = 6.5, 3.9 Hz, 1H), 3.73 - 3.57 (m, 2H), 3.36 (dd, J = 16.1, 8.3 Hz, 1H), 3.12 (dd, J = 16.1, 5.0 Hz, 1H), 2.89 (t, J = 7.1 Hz, 2H), 2.08 (s, 3H), 2.07 (s, 3H), 2.06 (s, 3H), 2.04 (s, 3H), 1.56 (s, 6H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-(2-(4-(2-(4-chlorobenzamido)ethyl)phenoxy)-2-methylpropanamido)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyltriacetate

[0366] (3) Compound 5c

[0367] 3.6 Hz, 1H), 5.32 (dd, J = 7.5, 3.3 Hz, 1H), 5.26 (dd, J = 5.0, 3.3 Hz, 1H), 5.14 (t, J = 6.9 Hz, 1H), 4.68 (dt, J = 8.2, 5.0 Hz, 1H), 4.40 (dd, J = 12.0, 6.6 Hz, 1H), 4.21 - 4.13 (m, 3H), 3.98 (td, J = 6.5, 3.8 Hz, 1H), 3.37 (dd, J = 16.2, 8.2 Hz, 1H), 3.14 (dd, J = 16.2, 5.1 Hz, 1H), 2.38 (s, 3H), 2.07 (s, 3H), 2.062 (s, 3H), 2.058 (s, 3H), 2.03 (s, 3H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(3-((5-(4-fluorophenyl)thiophen-2-yl)methyl)-4-methylphenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0368] (4) Compound 5d

[0369] J = 7.4, 3.3 Hz, 1H), 5.25 (dd, J = 5.2, 3.4 Hz, 1H), 5.14 (t, J = 6.8 Hz, 1H), 4.68 (dt, J = 9.1, 5.1 Hz, 1H), 4.41 (dd, J = 12.0, 6.7 Hz, 1H), 4.li (dd, J = 12.0, 3.9 Hz, 1H), 3.99 (td, J = 6.5, 3.9 Hz, 1H), 3.37 (dd, J = 16.1, 8.3 Hz, 1H), irl3 (dd, J = 16.1, 5.0 Hz, 1H), 2.87 (dd, J = 10.6, 8.4 Hz, 1H), 2.09 (s, 3H), 2.08 (s, 3H), 2.07 (s, 3H), 2.05 (s, 3H), 1.98 (dd, J = 10.7, 7.4 Hz, 1H), 1.81 (t, J = 7.9 Hz, 1H), 1.59 (s, 6H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-(2-(4-(2,2-dichlorocyclopropyl)phenoxy)-2-methylpropanamido)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0370] (5) Compound 5e

[0371] 7.25 (d, J = 7.8 Hz, 1H), 7.15 (td, J = 7.7, 1.6 Hz, 1H), 7.01 (t, J = 8.1 Hz, 1H), 6.96 (t, J = 7.4 Hz, 1H), 6.83 (s, 1H), 6.53 (d, J = 8.0 Hz, 1H), 5.31 (dd, J = 7.4, 3.3 Hz, 1H), 5.25 (dd, J = 5.1, 3.3 Hz, 1H), 5.13 (t, J = 6.9 Hz, 1H), 4.66 (dt, J = 8.2, 5.1 Hz, 1H), 4.40 (dd, J = 12.0, 6.7 Hz, 1H), 4.15 (dd, J = 12.1, 3.9 Hz, 1H), 3.98 (td, J = 6.6, 3.9 Hz, 1H), 3.87 (s, 2H), 3.34 (dd, J = 16.1, 8.2 Hz, 1H), 3.10 (dd, J = 16.2, 5.1 Hz, 1H), 2.07 (s, 3H), 2.06 (s, 3H), 2.05 (s, 3H), 2.03 (s, 3H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-(2-(2-((2,6-dichlorophenyl)amino)phenyl)acetamido)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0372] (6) Compound 5f

[0373] Hz,1H),4.35(dd,J=12.0,6.5Hz,1H),4.14(dd,J=12.0,3.8Hz,1H),3.95(td,J=6.6,3.8Hz,1H),3.35(dd,J=16.1,8.4Hz,1H),3.11(dd, J=16.1,5.1Hz,1H),3.01-2.87(m,2H),2.48(dd,J=18.5,8.7Hz,1H),2.44-2.38(m,1H),2.31(td,J=10.8,4.0Hz,1H),2.22-2.02(m,1H) ,2.06(s,6H),2.03(s,3H),2.02(s,3H),1.99-1.85(m,1H),1.68-1.38(m,6H),0.89(s,3H).(2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6- (2-((8R,9S,13S,14S)-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-yl)-2-oxoe thyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0374] The prior art (Nature, 2024, DOI: 10.1038 / s41586-024-07548-0) discloses a glycosyl thioether containing the -C5F4N functional group, which can be used for photocatalytic synthesis of glycosidic bonds. When the glycosyl thioether containing the -C5F4N functional group reacts with the drug of Example 5f to synthesize a carbon glycoside compound (compound 31 in the prior art), the yield is 77%, while the yield of the present invention is 88%, which is 14.3% higher than that of the prior art, indicating that the method of the present invention has a higher yield when used for such reactions. Furthermore, as shown in Example 9, the glycosyl thioether of the present invention can react with a variety of complex drugs, further broadening the range of reaction substrates.

[0375] (7) Compound 5g

[0376] The yield was 43%. Structural characterization data are as follows: 1 H

[0377] 3.4 Hz, 1H), 5.13 (t, J = 6.9 Hz, 1H), 4.66 (dt, J = 8.2, 5.0 Hz, 1H), 4.39 (dd, J = 12.0, 6.6 Hz, 1H), 4.15 (dd, J = 12.0, 3.9 Hz, 1H), 3.98 (td, J = 6.5, 3.9 Hz, 1H), 3.88 (d, J = 6.5 Hz, 2H), 3.37 (dd, J = 16.2, 8.2 Hz, 1H), 3.14 (dd, J = 16.2, 5.1 Hz, 1H), 2.76 (s, 3H), 2.16 (dq, J = 13.4, 6.6 Hz, 1H), 2.07 (s, 6H), 2.05 (s, 3H), 2.04 (s, 3H), 1.06 (d, J = 6.7 Hz, 6H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-(2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-carboxamido)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0378] (8) Compound 5h

[0379] Hz, 1H), 5.24 (dd, J = 5.5, 3.3 Hz, 1H), 5.12 (t, J = 6.5 Hz, 1H), 5.07 (hept, J = 6.3 Hz, 1H), 4.69 (dt, J = 8.4, 5.1 Hz, 1H), 4.44 (dd, J = 12.0, 6.9 Hz, 1H), 4.17 (dd, J = 12.1, 4.0 Hz, 1H), 4.00 (td, J = 6.5, 4.1 Hz, 1H), 3.42 (dd, J = 16.2, 8.5 Hz, 1H), 3.19 (dd, J = 16.2, 4.7 Hz, 1H), 2.09 (s, 3H), 2.08 (s, 6H), 2.05 (s, 3H), 1.65 (s, 6H), 1.19 (d, J = 6.3 Hz, 6H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-(4-((1-isopropoxy-2-methyl-1-oxopropan-2-yl)oxy)benzoyl)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0380] (9) Compound 5i

[0381] 5.22 (dd, J = 5.0, 3.4 Hz, 1H), 5.11 (t, J = 6.9 Hz, 1H), 4.63 (dt, J = 8.3, 5.1 Hz, 1H), 4.37 (dd, J = 12.0, 6.6 Hz, 1H), 4.12 (dd, J = 12.1, 3.8 Hz, 1H), 3.95 (td, J = 6.5, 3.8 Hz, 1H), 3.70 (q, J = 7.1 Hz, 1H), 3.32 (dd, J = 16.1, 8.2 Hz, 1H), 3.07 (dd, J = 16.2, 5.1 Hz, 1H), 2.44 (d, J = 7.2 Hz, 2H), 2.05 (s, 3H), 2.04 (s, 3H), 2.03 (s, 3H), 2.00 (s, 3H), 1.83 (dp, J = 13.5, 6.7 Hz, 1H), 1.55 (d, J = 7.1 Hz, 3H), 0.87 (d, J = 6.6 Hz, 6H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-(2-(4-isobutylphenyl)propanamido)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0382] (10) Compound 5j

[0383] 5.1 Hz, 1H), 4.37 (dd, J = 12.0, 6.6 Hz, 1H), 4.12 (dd, J = 12.0, 3.8 Hz, 1H), 3.95 (td, J = 6.6, 3.8 Hz, 1H), 3.78 (s, 2H), 3.76 (s, 3H), 3.31 (dd, J = 16.1, 8.2 Hz, 1H), 3.08 (dd, J = 16.2, 5.1 Hz, 1H), 2.40 (s, 3H), 2.052 (s, 3H), 2.046 (s, 3H), 2.03 (s, 3H), 2.01 (s, 3H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-(2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetamido)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyltriacetate

[0384] (11) Compound 5k

[0385] 1H), 7.06 (d, J = 8.3 Hz, 1H), 5.31 (dd, J = 7.5, 3.3 Hz, 1H), 5.25 (t, J = 4.1 Hz, 1H), 5.17 (s, 2H), 5.13 (t, J = 7.0 Hz, 1H), 4.65 (dt, J = 9.3, 5.3 Hz, 1H), 4.39 (dd, J = 12.1, 6.6 Hz, 1H), 4.14 (dd, J = 12.1, 3.8 Hz, 1H), 3.97 (q, J = 4.4, 2.7 Hz, 1H), 3.74 (s, 2H), 3.34 (dd, J = 16.1, 8.2 Hz, 1H), 3.10 (dd, J = 16.2, 5.0 Hz, 1H), 2.07 (s, 6H), 2.05 (s, 3H), 2.03 (s, 3H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-oxo-2-(4-(2-(11-oxo-6,11-dihydrodibenzo[b,e]oxepin-2-yl)acetamido)phenyl)ethyl)tetrahydro-2H-pyran-3,4,5-triyltriacetate

[0386] (12) Compound 5l

[0387] = 12.0, 6.6, 1.9 Hz, 1H), 4.17 - 4.05 (m, 3H), 3.94 (td, J = 6.6, 3.8 Hz, 1H), 3.78 (t, J = 12.4 Hz, 3H), 3.50 - 3.28 (m, 3H), 3.11 (dtd, J = 12.4, 9.0, 4.0 Hz, 3H), 2.86 (tt, J = 14.5, 5.1 Hz, 2H), 2.47 (ddd, J = 14.2, 9.3, 4.6 Hz, 1H), 2.40 - 2.22 (m, 3H), 2.045 (s, 3H), 2.037 (s, 3H), 2.02 (s, 3H), 1.98 (s, 3H) 1.21 (t, J = 7.1 Hz, 3H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(11-(1-(ethoxycarbonyl)piperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-8-yl)-2-oxoethyl)tetr ahydro-2H-pyran-3,4,5-triyl triacetate

[0388] (13) Compound 5m

[0389] (dd, J = 8.9, 2.6 Hz, 1H), 7.10 (d, J = 2.6 Hz, 1H), 5.29 (dd, J = 7.5, 3.4 Hz, 1H), 5.22 (dd, J = 5.1, 3.3 Hz, 1H), 5.12 (t, J = 7.0 Hz, 1H), 4.62 (dt, J = 8.1, 5.0 Hz, 1H), 4.37 (dd, J = 12.0, 6.6 Hz, 1H), 4.13 (dd, J = 12.1, 3.8 Hz, 1H), 3.95 (td, J = 6.6, 3.8 Hz, 1H), 3.89 (s, 3H), 3.84 (q, J = 7.1 Hz, 1H), 3.31 (dd, J = 16.1, 8.3 Hz, 1H), 3.06 (dd, J = 16.2, 5.1 Hz, 1H), 2.06 (s, 3H), 2.05 (s, 3H), 2.04 (s, 3H), 2.00 (s, 3H), 1.63 (d, J = 7.1 Hz, 3H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-((R)-2-(6-methoxynaphthalen-2-yl)propanamido)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0390] (14) Compound 5n

[0391] 5.24 (dd, J = 5.0, 3.4 Hz, 1H), 5.13 (t, J = 6.9 Hz, 1H), 4.65 (dt, J = 8.3, 5.1 Hz, 1H), 4.38 (dd, J = 12.0, 6.7 Hz, 1H), 4.15 (dd, J = 12.1, 3.8 Hz, 1H), 3.96 (td, J = 6.6, 3.9 Hz, 1H), 3.33 (dd, J = 16.2, 8.3 Hz, 1H), 3.27 (t, J = 6.7 Hz, 2H), 3.09 (dd, J = 16.1, 5.1 Hz, 1H), 2.97 (t, J = 6.8 Hz, 2H), 2.07 (s, 3H), 2.06 (s, 3H), 2.05 (s, 3H), 2.03 (s, 3H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-(3-(4,5-diphenyloxazol-2-yl)propanamido)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0392] (15) Compound 5o

[0393]

[0394] 5.1Hz,1H),4.60(dd,J=4.3,2.2Hz,1H),4.42(s,1H),4.41(dd,J=12.0,6.8Hz,1H),4.15(dd,J=12.0,4.0Hz,1H),3.97(td,J=6.5,4.0Hz,1H) ,3.49(dd,J=16.2,4.3Hz,1H),3.44(d,J=2.2Hz,1H),3.37(dd,J=16.4,8.4Hz,1H),3.15(dd,J=16.3,4.9Hz,1H),2.07(s,2H),2.065(s,3H), 2.058(s,3H),2.04(s,3H),1.56(s,3H),1.31(s,3H).(2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-((((2S,5R)-3,3-dimethyl-4,4-di oxido-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carbonyl)oxy)methyl)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0395] (16) Compound 5p

[0396] The yield was 66%. Structural characterization data were obtained using 1H NMR.

[0397] J = 8.6 Hz, 1H), 5.17 (dd, J = 8.9, 5.5 Hz, 1H), 4.99 (t, J = 8.6 Hz, 1H), 4.94 (q, J = 6.5 Hz, 1H), 4.22 (dd, J = 12.2, 5.3 Hz, 1H), 4.06 (dd, J = 12.2, 2.9 Hz, 1H), 3.93 (ddd, J = 8.5, 5.3, 2.9 Hz, 1H), 3.82 (s, 2H), 3.79 (s, 3H), 3.31 (dd, J = 16.3, 6.3 Hz, 1H), 3.20 (dd, J = 16.3, 7.0 Hz, 1H), 2.45 (s, 3H), 2.04 (s, 3H), 2.03 (s, 3H), 2.02 (s, 3H), 1.93 (s, 3H). (2R,3R,4R,5S,6R)-2-(acetoxymethyl)-6-(2-(4-(2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetamido)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyltriacetate

[0398] (17) Compound 5q

[0399] Hz, 1H), 6.70 (dd, J = 9.1, 2.5 Hz, 1H), 5.42 (t, J = 3.1 Hz, 1H), 5.34 (dd, J = 8.7, 4.8 Hz, 1H), 5.23 (dd, J = 8.7, 3.3 Hz, 1H), 4.95 (q, J = 6.2 Hz, 1H), 4.24 (dd, J = 10.8, 6.9 Hz, 1H), 4.17 - 4.12 (m, 1H), 4.09 (dd, J = 10.8, 4.9 Hz, 1H), 3.81 (s, 2H), 3.79 (s, 3H), 3.23 (dd, J = 16.5, 6.3 Hz, 1H), 3.15 (dd, J = 16.4, 6.7 Hz, 1H), 2.44 (s, 3H), 2.10 (s, 3H), 2.03 (s, 3H), 1.99 (s, 3H), 1.95 (s, 3H). (2R,3S,4R,5S,6R)-2-(acetoxymethyl)-6-(2-(4-(2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetamido)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0400] (18) Compound 5r

[0401] 3.0 Hz, 1H), 5.13 (t, J = 3.8 Hz, 1H), 4.99 (td, J = 6.5, - 2.3 Hz, 1H), 4.95 - - 4.91 (m, 1H), 4.51 (d, J = 2.4 Hz, 1H), 3.81 (s, 2H), 3.79 (s, 3H), 3.76 (s, - 3H), 3.36 (dd, J = 16.9, 6.1 Hz, 1H), 3.13 (dd, J = 17.0, 6.9 Hz, 1H), 2.44 (s, 3H), 2.12 (s, 3H), 2.08 (s, 3H), 2.04 (s, 3H). (2R, - 3S, 4R, 5S, - 6S)-2-(2-(4-(2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetamido)phenyl)-2-oxoethyl)-6-(methoxycarbonyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0402] (19) Compound 5s

[0403] 5.9 Hz, 1H), 4.92 (t, J = 5.1 Hz, 1H), 4.82 (dt, J = 8.3, 4.2 Hz, 1H), 4.39 (dd, J = 12.0, 6.7 Hz, 1H), 4.29 (ddd, J = 9.5, 6.3, 3.6 Hz, 1H), 4.23 (dd, J = 11.9, 4.9 Hz, 1H), 4.02 (dt, J = 6.6, 4.8 Hz, 1H), 3.22 (dd, J = 16.0, 8.4 Hz, 1H), 3.07 (dd, J = 16.0, 4 .7 Hz, 1H), 2.86 (dd, J = 10.7, 8.3 Hz, 1H), 2.12 (s, 3H), 2.10 (s, 3H), 2.04 (s, 3H), 2.00 (s, 3H), 1.97 (dd, J = 10.7, 7.5 Hz, 1H), 1.80 (t, J = 8.4, 7.4 Hz, 1H), 1.57 (s, 6H). (2R,3S,4R,5S,6R)-5-acetamido-2-(acetoxymethyl)-6-(2-(4-(2-(4-(2,2-dichlorocyclopropyl)phenoxy)-2-methylpropanamido)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4-diyl diacetate

[0404] (20) Compound 5t

[0405]

[0406] J = 6.9 Hz, 1H), 4.63 (dt, J = 8.6, 4.7 Hz, 1H), 3.84 (p, J = 6.5 Hz, 1H), 3.37 (dd, J = 16.3, 8.1 Hz, 1H), 3.10 (dd, J = 16.3, 5.1 Hz, 1H), 2.83 (dd, J = 10.7, 8.4 Hz, 1H), 2.05 (s, 6H), 2.02 (s, 3H), 1.94 (dd, J = 10.7, 7.4 Hz, 1H), 1.78 (t, J = 7.9 Hz, 1H), 1.55 (s, 6H), 1.26 (d, J = 6.5 Hz, 3H). (2S,3S,4R,5S,6S)-2-(2-(4-(2-(4-(2,2-dichlorocyclopropyl)phenoxy)-2-methylprop anamido)phenyl)-2-oxoethyl)-6-methyltetrahydro-2H-pyran-3,4,5-triyl triacetate

[0407] (21) Compound 5u

[0408]

[0409] 5.11 (t, J = 6.1 Hz, 1H), 4.57 (ddd, J = 7.3, 6.3, 4.5 Hz, 1H), 4.26 (dd, J = 11.8, 3.1 Hz, 1H), 4.18 (td, J = 4.7, 3.1 Hz, 1H), 4.12 (dd, J = = 16.8, 7.3 Hz, 1H), 3.22 (dd, J = 16.7, 4.5 Hz, 1H), 2.85 (dd, J = 10.7, 8.3 Hz, 1H), 2.08 (s, 3H), 2.06 (s, 6H), 1.96 (dd, J = 10.7, 7.5 Hz, 1H), 1.79 (dd, J = 8.3, 7.5 Hz, 1H), 1.57 (s, 6H). (2R,3R,4S,5S)-2-(acetoxymethyl)-5-(2-(4-(2-(4-(2,2-dichlorocyclopropyl)phenox y)-2-methylpropanamido)phenyl)-2-oxoethyl)tetrahydrofuran-3,4-diyl diacetate

[0410] (22) Compound 5v

[0411] (m, 1H), 4.17 - 4.06 (m, 2H), 3.33 (dd, J = 16.7, 6.1 Hz, 1H), 3.23 (dd, J = 16.7, 6.1 Hz, 1H), 2.85 (dd, J = 10.7, 8.3 Hz, 1H), 2.06 (s, 3H), 1.96 (dd, J = 10.7, 7.4 Hz, 1H), 1.80 (dd, J = 8.3, 7.5 Hz, 1H), 1.57 (s, 6H), 1.55 (s, 3H), 1.34 (s, 3H). ((3aR, 4R, 6S, 6aS)-6-(2-(4-(2-(4-(2,2-dichlorocyclopropyl)phenoxy)-2-methylpropanamido)phenyl)-2-oxoethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl acetate

[0412] (23) Compound 5w

[0413] Hz, 1H), 7.46 (td, J = 7.7, 1.4 Hz, 2H), 7.37 (d, J = 6.2 Hz, 1H), 7.07 (d, J = 8.5 Hz, 1H), 5.39 (dd, J = 9.5, 5.5 Hz, 1H), 5.28 (dd, J = 3.4, 2.2 Hz, 1H), 5.24 (dd, J = 9.5, 3.4 Hz, 1H), 5.19 (s, 2H), 4.97 (q, J = 6.2 Hz, 1H), 4.04 (qd, J = 6.4, 2.2 Hz, 1H), 3.75 (s, 2H), 3.30 (dd, J = 16.3, 6.3 Hz, 1H), 3.18 (dd, J = 16.3, 6.7 Hz, 1H), 2.14 (s, 3H), 2.01 (s, 3H), 1.92 (s, 2H), 1.13 (d, J = 6.5 Hz, 3H). (2S, 3R, 4R, 5R, 6S)-2-methyl-6-(2-oxo-2-(4-(2-(11-oxo-6,11-dihydrodibenzo[b,e]oxepin- - 2-yl)acetamido)phenyl)ethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0414] (24) Compound 5x

[0415] J = 7.4, 1.2 Hz, 1H), 7.07 (d, J = 8.5 Hz, 1H), 5.18 (s, 2H), 4.50 (q, J = 6.2 Hz, 1H), 4.31 - 4.14 (m, 2H), 4.03 (dd, J = 10.8, 7.2 Hz, 1H), 3.80 (dd, J = 10.9, 5.5 Hz, 1H), 3.75 (s, 2H), 3.67 (t, J = 10.5 Hz, 1H), 3.41 (td, J = 10.3, 5.5 Hz, 1H), 3.20 (d, J = 6.2 Hz, 2H), 1.50 (s, 6H), 1.41 (s, 3H), 1.35 (s, 3H). 2-(11-oxo-6,11-dihydrodibenzo[b,e]oxepin-2-yl)-N-(4-(2-((4R,5aR,9aR,9bR)-2,2,8,8-tetramethylhexahydro-[1,3]dioxolo[4',5':4,5]pyrano[3,2-d][1,3]dioxin-4-yl)acetyl)phenyl)acetamide

[0416] (Compound 5y)

[0417] =8.5Hz, 1H), 5.17 (s, 2H), 5.15 - 5.11 (m, 0.3H), 4.53 (dd, J=7.0, 4.6Hz, 0.7H), 4.48 (td, J=7.5, 4.4Hz, 0.3H), 4.38 (td, J=6.2, 4.6Hz, 0.7H), 4.28 (dd, J=7.0, 5.1Hz, 0.7H), 3.93 (dt, J=11.7, 6.3Hz, 0.7H), 3.88 (dd, J=7.8, 4.7Hz, 0.3H), 3.74 (s, 2H), 3.37 (dd, J=16.8, 7.2Hz, 0.3H), 3.29 (dd, J=16.6, 6.7Hz, 0.7H), 3.19 (dd, J=16.6, 5.8Hz, 0.7H), 3.13 (dd, J=16.9, 4.6Hz, 0.3H), 1.52 (s, 2H), 1.39 (s, 1.6H), 1.37 (d, J=6.4Hz, 0.9H), 1.32 (s, 2H), 1.26 (d, J=6.3Hz, 2.4H). 2-(11-oxo-6,11-dihydrodibenzo[b,e]oxepin-2-yl)-N-(4-(2-((3aS,4S,6R,6aR)-2,2,6-trimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)acetyl)phenyl)acetamide

[0418] (26) Compound of 5z

[0419] Hz,2H),6.92(d,J=8.6Hz,2H),6.32(t,J=5.9Hz,1H),4.82(dd,J=6.1,3.7H z,1H),4.70(d,J=6.9Hz,1H),4.64(dd,J=8.0,5.9Hz,1H),4.38(ddd,J=7.5 ,6.2,4.5Hz,1H),4.05(dd,J=8.8,6.3Hz,1H),3.97(dd,J=8.7,4.5Hz,1H), 3.85(dd,J=7.4,3.7Hz,1H),3.70-3.60(m,2H),3.20(dd,J=16.3,6.0Hz,1H) ,3.06(dd,J=16.3,8.1Hz,1H),2.88(t,J=7.1Hz,2H),1.55(s,6H),1.49(s, 3H),1.43(s,3H),1.35(s,3H),1.32(s,3H).(2R,3R,4R,5R,6R)-2-(acetox ymethyl)-6-(2-(4-(2-(4-(2-(4-chlorobenzamido)ethyl)phenoxy)-2-methylpropanamido)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-tr iyltriacetate

[0420] Example 10: Application of glycosyl thioethers in the synthesis of C-glycosides

[0421] In this embodiment, a series of visible-light-catalyzed β-carbonyl-α-alkyl C-glycosides were synthesized using glycosyl thioethers as glycosyl radical donors and styryl polypeptides as glycosyl acceptors. The synthetic method includes the following steps:

[0422]

[0423] I. Synthesis of Compound 6

[0424] The method is the same as in Example 8, except that the olefin glycosyl receptor is replaced with a styrene polypeptide, and the amount of styrene polypeptide is 1.0 eq., 0.15 mmol.

[0425] II. Structure and Characterization of Compounds

[0426] (1) Compound 6a

[0427] 4.9, 3.3 Hz, 1H), 5.13 (t, J = 7.1 Hz, 1H), 4.65 (dt, J = 8.3, 5.0 Hz, 1H), 4.60 - 4.51 (m, 1H), 4.38 (dd, J = 12.0, 6.6 Hz, 1H), 4.14 (dd, J = 12.0, 3.9 Hz, 1H), 3.97 (td, J = 6.6, 3.8 Hz, 1H), 3.35 (dd, J = 16.1, 8.3 Hz, 1H), 3.23 - 2.96 (m, 3H), 2.08 (s, 3H), 2.07 (s, 3H), 2.06 (s, 3H), 2.03 (s, 3H), 1.44 (s, 9H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-((S)-2-((tert-butoxycarbonyl)oxy)-3-methoxy-3-oxopropyl)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0428] (2) The yield of compound 6b was 76%. The structure characterization data were: 1H NMR

[0429] 7.3 Hz,​

[0430] (3) Compound 6c

[0431] 1H), 5.00 (s, 1H), 4.67 (dt, J = 8.4, 5.0 Hz, 1H), 4.49 - 4.35 (m, 2H), 4.41 (dd, J = 12.0, 6.7 Hz, 1H), 4.15 (dd, J = 12.0, 4.0 Hz, 1H), 4.04 (dd, J = 18.2, 5.4 Hz, 1H), 4.01 - 3.91 (m, 2H), 3.74 (s, 3H), 3.36 (dd, J = 16.2, 8.4 Hz, 1H), 3.25 - 3.06 (m, 3H), 2.09 (s, 3H), 2.08 (s, 3H), 2.07 (s, 3H), 2.05 (s, 3H), 1.40 (s, 9H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-((S)-2-((tert-butoxycarbonyl)oxy)-3-methoxy-3-oxopropyl)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyltriacetate

[0432] (4) Compound 6d

[0433] J = 6.7 Hz, 1H), 5.02 - 4.98 (m, 1H), 4.67 (dt, J = 8.4, 5.0 Hz, 1H), 4.47 (dd, J = 8.7, 4.9 Hz, 1H), 4.41 (dd, J = 12.0, 6.7 Hz, 1H), 4.42 - 4.32 (m, 1H), 4.17 (dd, J = 12.0, 4.0 Hz, 1H), 3.98 (td, J = 6.5, 3.9 Hz, 1H), 3.70 (s, 3H), 3.37 (dd, J = 16.2, 8.4 Hz, 1H), 3.23 - 3.05 (m, 3H), 2.17 - 2.05 (m, 1H), 2.09 (s, 3H), 2.08 (s, 3H), 2.07 (s, 3H), 2.06 (s, 3H), 1.42 (s, 9H), 0.89 (d, J = 6.9 Hz, 3H), 0.86 (d, J = 6.8 Hz, 3H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-((S)-2-((tert-butoxycarbonyl)amino)-3-(((S)-1-methoxy-3-methyl-1-oxobutan-2-yl)amino)-   3-oxopropyl)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyltriacetate

[0434] (5) Compound 6e

[0435] 7.3 Hz, 1H), 5.00 (s, 1H), 4.67 (dt, J = 8.3, 5.0 Hz, 1H), 4.57 (td, J = 8.6, 4.8 Hz, 1H), 4.41 (dd, J = 12.0, 6.7 Hz, 1H), 4.42 - 4.29 (m, 1H), 4.16 (dd, J = 12.0, 4.0 Hz, 1H), 3.98 (td, J = 6.5, 3.9 Hz, 1H), 3.70 (s, 3H), 3.37 (dd, J = 16.2, 8.4 Hz, 1H), 3.23 - 3.03 (m, 3H), 2.09 (s, 3H), 2.08 (s, 3H), 2.07 (s, 3H), 2.06 (s, 3H), 1.65 - 1.55 (m, 2H), 1.55 - 1.45 (m, 1H), 1.41 (s, 9H), 0.91 (t, J = 6.1 Hz, 6H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-((S)-2-((tert-butoxycarbonyl)amino)-3-(((S)-1-methoxy-4-methyl-1-oxopentan-2-yl)amino)-3-oxopropyl)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyltriacetate

[0436] (6) Compound 6f

[0437] 2H), 4.66 (dt, J = 8.3, 5.1 Hz, 1H), 4.63 - 4.57 (m, 1H), 4.44 - 4.31 (m, 2H), 4.15 (dd, J = 12.0, 3.9 Hz, 1H), 3.98 (td, J = 6.6, 3.9 Hz, 1H), 3.91 (s, 2H), 3.76 (s, 3H), 3.35 (dd, J = 16.0, 8.3 Hz, 1H), 3.24 - 3.09 (m, 2H), 2.09 (s, 3H), 2.08 (s, 3H), 2.06 (s, 3H), 2.06 (s, 3H), 1.41 (s, 9H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-((S)-2-((tert-butoxycarbonyl)amino)-3-(((S)-3-hydroxy-1-methoxy-1-oxopropan-2-yl)amino)-3-oxopropyl)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0438] (7) Compound 6g

[0439] Hz, 1H), 5.19 - 5.04 (m, 2H), 4.74 (q, J = 6.2 Hz, 1H), 4.68 (dt, J = 9.3, 5.1 Hz, 1H), 4.45 - 4.33 (m, 2H), 4.16 (dd, J = 12.1, 3.8 Hz, 1H), 3.99 (td, J = 6.5, 3.7 Hz, 1H), 3.69 (s, 3H), 3.36 (dd, J = 16.4, 8.2 Hz, 1H), 3.23 - 3.09 (m, 2H), 3.06 - 2.89 (m, 3H), 2.08 (s, 6H), 2.06 (s, 3H), 2.05 (s, 3H), 1.41 (s, 9H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-((S)-2-((tert-butoxycarbonyl)amino)-3-(((S)-3-(4-hydroxyphenyl)-1-methoxy-1-oxopropan-2-yl)amino)-3-oxopropyl)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyltriacetate

[0440] (8) Compound 6h

[0441] 2H), 4.66 (dt, J = 8.3, 5.1 Hz, 1H), 4.54 (dd, J = 8.9, 2.6 Hz, 1H), 4.43 (q, J = 7.0 Hz, 1H), 4.38 (dd, J = 12.0, 6.7 Hz, 1H), 4.33 - 4.27 (m, 1H), 4.15 (dd, J = 12.0, 3.9 Hz, 1H), 3.98 (td, J = 6.6, 3.9 Hz, 1H), 3.74 (s, 3H), 3.35 (dd, J = 16.0, 8.3 Hz, 1H), 3.25 - 3.10 (m, 3H), 2.44 (s, 1H), 2.09 (s, 3H), 2.08 (s, 3H), 2.062 (s, 3H), 2.056 (s, .....

[0442] (9) Compound 6i

[0443] 6.8 Hz, 1H), 4.98 (s, 1H), 4.72 - 4.60 (m, 2H), 4.41 (dd, J = 12.0, 6.7 Hz, 1H), 4.41 - 4.32 (m, 1H), 4.16 (dd, J = 12.0, 4.0 Hz, 1H), 3.98 (td, J = 6.5, 3.9 Hz, 1H), 3.72 (s, 3H), 3.38 (dd, J = 16.2, 8.4 Hz, 1H), 3.22 - 3.07 (m, 3H), 2.48 - 2.38 (m, 2H), 2.18 - 2.09 (m, 1H), 2.09 (s, 3H), 2.08 (s, 3H), 2.07 (s, 3H), 2.062 (s, 3H), 2.058 (s, 3H), 1.99 - 1.88 (m, 1H), 1.42 (s, 9H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-((S)-2-((tert-butoxycarbonyl)amino)-3-(((S)-1-methoxy-4-(methylthio)-1-oxobutan-2-yl)amino)-3-oxopropyl)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0444] (10) Compound 6j

[0445] 6.8 Hz, 1H), 5.01 (d, J = 8.2 Hz, 1H), 4.67 (dt, J = 8.3, 5.0 Hz, 1H), 4.51 (dd, J = 8.5, 5.0 Hz, 1H), 4.41 (dd, J = 12.0, 6.7 Hz, 1H), 4.41 - 4.29 (m, 1H), 4.16 (dd, J = 12.0, 4.0 Hz, 1H), 3.98 (td, J = 6.5, 3.9 Hz, 1H), 3.69 (s, 3H), 3.37 (dd, J = 16.2, 8.3 Hz, 1H), 3.23 - 3.05 (m, 3H), 2.09 (s, 3H), 2.08 (s, 3H), 2.07 (s, 3H), 2.06 (s, 3H), 1.85 (ddt, J = 9.5, 7.0, 4.8 Hz, 1H), 1.42 (s, 9H), 1.42 - 1.30 (m, 1H), 1.11 (ddt, J = 14.1, 9.0, 7.2 Hz, 1H), 0.89 (t, J = 7.4 Hz, 3H), 0.84 (d, J =6.9 Hz, 3H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-((S)-2-((tert-butoxycarbonyl)amino)-3-(((2S,3R)-1-methoxy-3-methyl-1-oxopentan-2-yl)amino)-3-oxopropyl)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyltriacetate

[0446] (11) Compound 6k

[0447] Hz, 1H), 5.13 (t, J = 7.3 Hz, 1H), 4.99 (d, J = 7.9 Hz, 1H), 4.79 (dt, J = 8.4, 4.4 Hz, 1H), 4.67 (dt, J = 8.4, 5.0 Hz, 1H), 4.41 (dd, J = 12.0, 6.7 Hz, 1H), 4.16 (dd, J = 12.0, 4.0 Hz, 1H), 3.98 (td, J = 6.5, 4.0 Hz, 1H), 3.73 (s, 3H), 3.66 (s, 3H), 3.37 (dd, J = 16.2, 8.4 Hz, 1H), 3.20 (dd, J = 13.9, 6.1 Hz, 1H), 3.17 - 3.06 (m, 2H), 3.01 (dd, J = 17.3, 4.4 Hz, 1H), 2.82 (dd, J = 17.3, 4.6 Hz, 1H), 2.09 (s, 3H), 2.08 (s, 3H), 2.07 (s, 3H), 2.06 (s, 3H), 1.41 (s, 9H). Dimethyl ((S)-2-((tert-butoxycarbonyl)amino)-3-(4-(2-((2R,3R,4R,5R,6R)-3,4,5-triacetoxy-6-(acetoxymethyl)tetrahydro-2H-pyran-2-yl)acetyl)phenyl)propanoyl)-L-aspartate

[0448] (12) Compound 6l

[0449] Hz, 1H), 5.24 (dd, J = 5.3, 3.3 Hz, 1H), 5.13 (t, J = 6.7 Hz, 1H), 4.95 (s, 1H), 4.79 (q, J = 6.4 Hz, 1H), 4.67 (dt, J = 8.4, 5.1 Hz, 1H), 4.40 (dd, J = 12.0, 6.7 Hz, 1H), 4.37 - 4.32 (m, 1H), 4.16 (dd, J = 12.0, 4.0 Hz, 1H), 3.97 (td, J = 6.5, 4.0 Hz, 1H), 3.68 (s, 3H), 3.36 (dd, J = 16.2, 8.4 Hz, 1H), 3.18 - 2.99 (m, 5H), 2.09 (s, 3H), 2.07 (s, 6H), 2.05 (s, 3H), 1.40 (s, 9H). (2R,3R,4R,5R,6R)-2-(acetoxymethyl)-6-(2-(4-((S)-2-((tert-butoxycarbonyl)amino)-3-(((S)-1-methoxy-1-oxo-3-phenylpropan-2-yl)amino)-3-oxopropyl)phenyl)-2-oxoethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0450] (13) Compound 6m

[0451] 1H),5.31(dd,J=7.4,3.3Hz,1H),5.25(t,J=4.2Hz,1H),5.14(t,J=6.9Hz,1H),5. 09(d,J=8.5Hz,1H),4.82(dt,J=8.0,5.5Hz,1H),4.67(dt,J=8.3,5.0Hz,1H),4.41 (dd,J=12.1,6.7Hz,1H),4.38-4.32(m,1H),4.16(dd,J=12.1,3.8Hz,1H),3.99(t d,J=6.5,3.7Hz,1H),3.65(s,3H),3.32(dd,J=16.3,8.4Hz,1H),3.28-3.17(m,2H) ,3.09(dd,J=16.3,4.9Hz,1H),3.05-2.95(m,2H),2.075(s,3H),2.067(s,3H),2. 06(s,3H),2.03(s,3H),1.37(s,9H).(2R,3R,4R,5R,6R)-2-(2-(4-((S)-3-(((S)- 3-(1H-indol-2-yl)-1-methoxy-1-oxopropan-2-yl)amino)-2-((tert-butoxycarbonyl)amino)-3-oxopropyl)phenyl)-2-oxoethyl)-6-(acetoxymethyl)tetrah ydro-2H-pyran-3,4,5-triyl triacetate

[0452] As can be seen from the above embodiments, this invention designs and synthesizes a glycosyl thioether with an oxime functional group and applies it to the synthesis of C-glycosides mediated by glycosyl radicals. Using the glycosyl thioether with an oxime functional group as a glycosyl radical donor and styrene compounds as glycosyl acceptor substrates, a visible-light-catalyzed method for the synthesis of β-carbonyl-α-alkyl C-glycosides was established, resulting in the synthesis of a series of C-glycoside compounds. The glycosyl thioether prepared by this invention is stable, and its preparation method has the advantages of being simple, having high yield, and being applicable to a wide range of sugars. Applying it to the synthesis of C-glycosides offers advantages such as simplicity and a wide range of substrates, including various drugs and peptides. This indicates that the glycosyl thioether provides a new approach for the development of complex glycoconjugates and drugs, further promoting the industrialization of C-glycoside pharmaceuticals.

Claims

1. The compound represented by Formula I, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a solvate thereof, or a crystal form thereof, wherein the compound has the following structural formula: in, The sugar is selected from monosaccharides protected by hydroxyl groups; The hydroxyl protecting group is selected from at least one of ether protecting groups, ester protecting groups, acetal protecting groups, benzylidene protecting groups, or acetone protecting groups.

2. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a solvate thereof, or a crystal form thereof, characterized in that, The monosaccharide is selected from substituted or unsubstituted monosaccharides, and the substituent is selected from methyl, methoxy, and C6 aryl groups; And / or, the hydroxyl protecting group is selected from at least one of acetyl, tert-butyldiphenylsilane ether, acetone ide, and benzyl ide protecting groups.

3. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a solvate thereof, or a crystal form thereof, characterized in that, The structural formula of the compound shown in Formula I is:

4. A method for preparing the compound according to any one of claims 1-3, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a solvate thereof, or a crystal form thereof, characterized in that, Includes the following steps: Step 1: Compound 1 reacts with a reducing agent in the presence of a co-catalyst to obtain compound 2; Step 2: Add an alkali and an acylation reagent to compound 2, and stir to obtain the final product.

5. The preparation method according to claim 4, characterized in that: The co-catalyst is sodium acetate, the reducing agent is hydroxylamine hydrochloride, and the reaction is carried out in a mixed solvent of ethanol / water with a volume ratio of 1-4:1, under reflux at 98-102°C for 4-8 hours. And / or, the base is triethylamine or pyridine, and the acylation reagent is trifluoromethylbenzoyl chloride; the stirring is carried out at 0-4°C for 1-2 hours.

6. The preparation method according to claim 4, characterized in that, Compound 1 is prepared by steps comprising at least one of the following six pathways: Route 1: Add a reducing agent and a Lewis acid catalyst to a monosaccharide protected by all hydroxyl groups, and react at 20-25℃ to obtain the product; Route 2 involves adding a strong base catalyst and a brominated monosaccharide to the reducing agent and reacting it at 20-25°C to obtain the product. Route 3: The compound obtained by any one of routes 1 and 2 is mixed with a strong base and reacted at 20-25℃ for 20-30 minutes. A neutralizing agent is added, the pH is adjusted to 5-7, filtered, and the filtrate is reacted with a monohydroxyl protecting agent at 20-25℃ to obtain the final product. The following paths can be selected according to the type of raw sugar: Route 4: The compound prepared by any one of routes 1 or 2 of the six-membered ring monosaccharide with full hydroxyl protection is mixed with a strong base and reacted at 20-25°C for 20-30 minutes. A neutralizing agent is added, the pH is adjusted to 5-7, filtered, and the filtrate is reacted with a dihydroxyl protecting agent at 20-25°C to obtain the product. Route 5: The compound obtained by preparing the five-membered ring monosaccharide with all-hydroxyl protection according to the steps described in Route 4 is mixed with an organic base catalyst, and after adding an acetylation reagent, it is reacted at 20-25°C to obtain the product. Route 6: A monosaccharide with one exposed hydroxyl group is mixed with an organic base catalyst, and an acetylation reagent is added. The mixture is then reacted at 20-25°C for 6-10 hours. A bromination reagent is added to the product, and the mixture is reacted at 20-25°C for 5-8 hours to obtain a brominated monosaccharide. The process is then repeated according to the steps of Route 2 to obtain the final product. The reducing agent is 2-mercaptoacetophenone, the Lewis acid catalyst is boron trifluoride diethyl ether, the strong base catalyst is potassium tert-butoxide, the strong base is sodium methoxide or triethylamine, the neutralizing agent is Amberlite H+ resin, the organic base catalyst is 4-dimethylaminopyridine, the acetylation agent is acetic anhydride, and the bromination agent is trimethylbromosilane. The monohydroxyl protecting agent is selected from tert-butyldiphenylchlorosilane, trimethylchlorosilane, triethylchlorosilane, triisopropylchlorosilane, tert-butyldimethylchlorosilane, triphenylmethyl ether, and tetrahydropyran; the dihydroxyl protecting agent is 2,2-dimethoxypropane and benzaldehyde dimethyl acetal.

7. Use of the compound of any one of claims 1-3, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a solvate thereof, or a crystal form thereof, for the preparation of glycoside compounds and / or glycoside drugs and / or glycoside vaccines.

8. The compound represented by Formula II, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a solvate thereof, or a crystal form thereof, has the following structural formula: in, The sugar is selected from monosaccharides protected by hydroxyl groups. The hydroxyl protecting group is selected from at least one of ether protecting groups, ester protecting groups, acetal protecting groups, benzylidene protecting groups, or acetone protecting groups; Ar is selected from C6-C that is substituted with 1-3 R1 atoms or is unsubstituted. 10 Aromatic rings, 5-9 membered aromatic heterocycles substituted with or unsubstituted with 1-3 R1 groups, and C2 alkenyl groups substituted with or unsubstituted with 1-3 R1 groups; R1 is independently selected from C6-C. 10 Aromatic rings, C1-C 10 Alkyl, C1-C 10 alcohols, C1-C 10 Alkoxy, C6-C 10 aryloxy group, substituted or unsubstituted C2-C 10 Ester group, substituted or unsubstituted C2-C 10 Amide, C1-C 10 Alkylthio, halogen, substituted C2 boron ester, substituted or unsubstituted C1-C 10 Acyl groups, substituted C2-olefin groups, N-protected oligopeptides, and drug molecules; Alternatively, two R1s may be linked together to form substituted or unsubstituted 5-9 membered heterocyclic alkyl groups; The substituents are selected from 5-9 membered aromatic heterocycles, N-protected 5-9 membered heterocycles, N-protected amino groups, and C1-C... 10 Alkyl, C6-C 10 Aromatic rings; The drug molecule is selected from carboxyl-containing drugs and halogen-substituted C6-C drugs. 10 Aromatic ring drugs, hydroxyl-substituted C6-C 10 Aromatic ring drugs.

9. The compound according to claim 8, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a solvate thereof, or a crystal form thereof, characterized in that, The compound shown in Formula II has the following structural formula:

10. A method for preparing the compound of any one of claims 8 and 9, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a solvate thereof, or a crystal form thereof, characterized in that, Includes the following steps: By mixing raw material A and raw material B, we obtain... Sugar, Ar, and R1 are as described in any one of claims 8 and 9.

11. The preparation method according to claim 10, characterized in that, The specific steps include the following: At 20-25℃, raw material A is mixed with catalyst and raw material B, and reacted under 450-460nm light for 3-6 hours to obtain the product. The catalyst is Ir(ppy)3.

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