Imidazole alkenyl sulfur reagent, synthesis method thereof and application of imidazole alkenyl sulfur reagent in selective construction of thioglycoside compounds

Abstract

The invention discloses an imidazole alkenyl sulfur reagent as well as a synthesis method and application thereof in selective construction of thioglycoside compounds, and the method comprises the following steps: taking a compound as shown in a formula (1) and isopropyl thiourea as shown in a formula (2) as reaction raw materials, and reacting in an organic solvent to obtain the imidazole alkenyl sulfur reagent as shown in a formula (6); the thioglycoside compound is obtained by taking a carbohydrate compound as shown in a formula (7) and an imidazole alkenyl sulfur reagent as shown in a formula (6) as reaction raw materials and reacting in an organic solvent under the action of alkali. The method has the advantages of mild reaction conditions, cheap and easily available raw materials, simple reaction operation, and high yield and selectivity; reaction substrates are easy to prepare; the reaction disclosed by the invention can be used for constructing a novel imidazole alkenyl sulfur reagent and a thioglycoside compound, and has wide application prospect and practical value.

Description

Technical Field

[0001] The invention belongs to the technical field of organic compound process application, and particularly relates to an imidazolyl sulfide reagent and a synthesis method thereof, and application thereof in the selective construction of glucosidic compounds. Background Art

[0002] Glucosides are widely found in natural products and pharmaceuticals, and their synthesis has long attracted considerable attention. While scientists have devised a variety of glycosylation methods, existing preparation methods share a common drawback: they require pre-functionalization of the raw materials and require a multi-step synthesis catalyzed by transition metals, resulting in lengthy, time-consuming, and reagent-intensive synthetic routes.

[0003] Therefore, it is particularly important to find a universal, efficient, environmentally friendly, mild and economical method for synthesizing glucosinolates. Summary of the Invention

[0004] To overcome the limitations of traditional glucosinolate synthesis, the present invention utilizes an imidazolyl thiolate reagent. This reaction is highly efficient and selective, requiring no pre-functionalization of the reaction substrate or the presence of a transition metal. It directly utilizes readily available raw materials to yield diverse, stereospecific glucosinolate compounds. In light of this, the present invention proposes a method for preparing an imidazolyl thiolate reagent by reacting an alkenyl Grignard reagent with another molecule of imidazole thiourea. Furthermore, a method for preparing a glucosinolate compound by reacting an imidazolyl thiolate reagent with another molecule of a carbohydrate in the presence of a base is also disclosed.

[0005] The present invention provides an imidazolyl sulfide reagent compound, the structural formula of which is shown in formula (6):

[0006]

[0007] in,

[0008] R 1 is selected from alkenyl and substituted alkenyl; wherein the substituted alkenyl is selected from alkyl substituted alkenyl.

[0009] Preferably,

[0010] R 1 is selected from alkenyl and substituted alkenyl; wherein the substituted alkenyl is selected from C1-C19 alkyl substituted alkenyl;

[0011] More preferably,

[0012] R 1 Selected from alkenyl and substituted alkenyl; wherein the substituted alkenyl is selected from ethylene, 2-propylene, cyclohexene, cycloheptene, and sterol.

[0013] Furthermore, the imidazolyl sulfide reagent represented by formula (6) of the present invention is shown in Table 1.

[0014] The present invention also provides a method for synthesizing an imidazolyl sulfide reagent, comprising the following steps:

[0015] Step (1): using 3-hydroxy-2-butanone represented by formula (1) and isopropylthiourea represented by formula (2) as reaction materials, reacting in a first organic solvent to obtain a compound represented by formula (3);

[0016] Step (2): In a second organic solvent, the compound represented by formula (3) reacts with liquid bromine to obtain a compound represented by formula (4);

[0017] Step (3): In a third organic solvent, the compound represented by formula (4) and the compound represented by formula (5) react with NaSbF6 to obtain an imidazole sulfide reagent represented by formula (6); the reaction process is shown in reaction formula (a);

[0018]

[0019] in,

[0020] R 1 is selected from alkenyl and substituted alkenyl; wherein the substituted alkenyl is selected from alkyl substituted alkenyl.

[0021] Preferably,

[0022] R 1 is selected from alkenyl and substituted alkenyl; wherein the substituted alkenyl is selected from C1-C19 alkyl substituted alkenyl;

[0023] More preferably,

[0024] R 1 Selected from alkenyl and substituted alkenyl; wherein the substituted alkenyl is selected from ethylene, 2-propylene, cyclohexene, cycloheptene, and sterol.

[0025] In step (1):

[0026] The ratio of the 3-hydroxy-2-butanone represented by formula (1), the isopropylthiourea represented by formula (2) and the first organic solvent is 1 mol: (1-3) mol: (5-10) volumes; preferably, 1 mol: 1 mol: 10 volumes;

[0027] The first organic solvent is selected from one or more of n-hexanol, dichloromethane, tetrahydrofuran, etc.; preferably, n-hexanol;

[0028] The reaction temperature is 0-160°C; preferably, the reaction temperature is 160°C;

[0029] The reaction time is 3-16 hours; preferably, the reaction time is 16 hours;

[0030] In step (2):

[0031] The ratio of the imidazole thiourea represented by formula (3), liquid bromine and the second organic solvent is 1 mol: (1-3) mol: (5-10) volume; preferably, 1 mol: 1 mol: 10 volume;

[0032] The second organic solvent is selected from one or more of n-hexanol, dichloromethane, tetrahydrofuran, etc.; preferably, dichloromethane;

[0033] The reaction temperature is 0°C to room temperature; preferably, room temperature;

[0034] The reaction time is 1-6 hours; preferably, 3 hours;

[0035] In step (3):

[0036] The usage ratio of the bromoimidazole sulfonate represented by formula (4), the alkenyl formaldehyde test represented by formula (5), NaSbF6, and the third organic solvent is 1 mol: (1-3) mol: (1-5) mol: (5-10) volume; preferably, it is 1 mol: 1 mol: 3 mol: 10 volume.

[0037] The third organic solvent is selected from one or more of n-hexanol, dichloromethane, tetrahydrofuran, etc.; preferably, it is tetrahydrofuran.

[0038] The reaction temperature is 0-room temperature; preferably, 25°C;

[0039] The reaction time is 1-16 hours; preferably, 16 hours.

[0040] In the present invention, in reaction formula (a), the reaction is carried out in a nitrogen atmosphere.

[0041] The present invention also proposes the use of the imidazolyl sulfide reagent in the selective construction of glucosinolate compounds, wherein the saccharide compound represented by formula (7) and the imidazolyl sulfide reagent represented by formula (6) are used as reaction raw materials, and under the action of a base, in an organic solvent, a glucosinolate compound represented by formula (8) is obtained by reaction, and the reaction process is shown in reaction formula (b):

[0042]

[0043] in,

[0044] R is selected from benzyl, acyl, alkyl, and silicon; R 1is selected from alkenyl and substituted alkenyl; wherein the substituted alkenyl is selected from alkyl substituted alkenyl; n is an integer selected from 1 to 100;

[0045] Preferably,

[0046] R is selected from benzyl, alkyl acyl, isopropyl, tert-butyldiphenylsilyl; R 1 is selected from alkenyl and substituted alkenyl; wherein the substituted alkenyl is selected from C1-C19 alkyl substituted alkenyl; n is an integer selected from 1-10;

[0047] More preferably,

[0048] R is selected from benzyl, acetyl, isopropyl, tert-butyldiphenylsilyl; R 1 is selected from alkenyl and substituted alkenyl; wherein the substituted alkenyl is selected from ethylene, 2-propylene, cyclohexene, cycloheptene, and sterol; and n is selected from an integer of 4-6.

[0049] In the present invention, in reaction formula (b), the base is selected from one or more of sodium carbonate, potassium carbonate, cesium carbonate, potassium tert-butoxide, lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide monohydrate, pyridine, 2,6-lutidine, 2,4,6-trimethylpyridine, triethylamine, diisopropylethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), tetramethylguanidine (TMG), 2-tert-butyl-1,1,3,3-tetramethylguanidine (BTMG), etc.; preferably, one or two selected from 2-tert-butyl-1,1,3,3-tetramethylguanidine (BTMG), cesium hydroxide monohydrate, etc.

[0050] In the present invention, in reaction formula (b), the organic solvent is selected from one or more of dichloromethane, toluene, tetrahydrofuran, nitromethane, toluene, chloroform, acetone, N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), acetonitrile, ethyl acetate, etc.; preferably, it is acetone.

[0051] In the present invention, in reaction formula (b), the reaction temperature is -78 to 50°C; preferably, 25°C

[0052] In the present invention, in reaction formula (b), the reaction time is 8-24 hours; preferably, 16 hours.

[0053] In the present invention, in reaction formula (b), the ratio of the carbohydrate compound, the base, the imidazolyl sulfide reagent and the organic solvent is 1 mol: (1.5-7) mol: (1.5-3) mol: (5-10) volume; preferably, it is 1 mol: 7 mol: 2 mol: 10 volume.

[0054] In the present invention, in reaction formula (b), the reaction is carried out in an air atmosphere.

[0055] The present invention also provides a glucosidoglycoside compound, the structural formula of which is shown in formula (8):

[0056]

[0057] in,

[0058] R is selected from benzyl, acyl, alkyl, and silicon; R 1 is selected from alkenyl and substituted alkenyl; wherein the substituted alkenyl is selected from alkyl substituted alkenyl; n is an integer selected from 1 to 100;

[0059] Preferably,

[0060] R is selected from benzyl, alkyl acyl, isopropyl, tert-butyldiphenylsilyl; R 1 is selected from alkenyl and substituted alkenyl; wherein the substituted alkenyl is selected from C1-C19 alkyl substituted alkenyl; n is an integer selected from 1-10;

[0061] More preferably,

[0062] R is selected from benzyl, acetyl, isopropyl, tert-butyldiphenylsilyl; R 1 is selected from alkenyl and substituted alkenyl; wherein the substituted alkenyl is selected from ethylene, 2-propylene, cyclohexene, cycloheptene, and sterol; and n is selected from an integer of 4-6.

[0063] Furthermore, the glucosinolate compounds represented by formula (8) of the present invention are shown in Table 2.

[0064] The present invention also proposes the use of the glucosinolate compound in constructing a glucosinolate-labeled protein, wherein the glucosinolate compound shown in formula (8) is used as a reaction raw material, and under the action of an oxidant, in an organic solvent, a reaction is performed to obtain an oxidized glucosinolate compound shown in formula (9); then, under the action of a photosensitizer, in a solvent, a reaction is performed to obtain a glucosinolate-labeled protein shown in formula (10), and the reaction process is shown in reaction formula (c):

[0065]

[0066] in,

[0067] R is selected from benzyl, acyl, alkyl, and silicon; R 1 is selected from alkenyl, substituted alkenyl; wherein the substituted alkenyl is selected from alkyl substituted alkenyl; wherein the substituted alkenyl is selected from alkyl substituted alkenyl; n is an integer selected from 1-100;

[0068] Preferably,

[0069] R is selected from benzyl, alkyl acyl, isopropyl, tert-butyldiphenylsilyl; R 1is selected from alkenyl and substituted alkenyl; wherein the substituted alkenyl is selected from C1-C19 alkyl substituted alkenyl; n is an integer selected from 1-10;

[0070] More preferably,

[0071] R is selected from benzyl, acetyl, isopropyl, tert-butyldiphenylsilyl; R 1 is selected from alkenyl and substituted alkenyl; wherein the substituted alkenyl is selected from ethylene, 2-propylene, cyclohexene, cycloheptene, and sterol; and n is selected from an integer of 4-6.

[0072] In the present invention, in reaction formula (c), the ratio of the glucosinolate compound represented by formula (8), the oxidant, and the organic solvent is 1 mol:(2-3) mol:(5-10) volumes, preferably 1 mol:2.5 mol:10 volumes.

[0073] In the present invention, in reaction formula (c), the oxidant is selected from one or more of hydrogen peroxide, meta-chloroperbenzoic acid, etc.; preferably, it is meta-chloroperbenzoic acid.

[0074] In the present invention, in reaction formula (c), the amount ratio of the oxidized sulfosuccinate compound represented by formula (9), ribonuclease A, the photosensitizer and the solvent is (10-100) mol:1 mol:(1-10) mol:(10-1000) volume; preferably, it is 10 mol:1 mol:1 mol:1000 volume.

[0075] In the present invention, in reaction formula (c), the organic solvent is selected from one or more of chloroform, dichloromethane, methanol, ethanol, etc.; preferably, it is dichloromethane.

[0076] In the present invention, in reaction formula (c), the photosensitizer is selected from one or more of flavin, rose bengal, rhodamine, iridium trichloride, etc.; preferably, it is flavin.

[0077] In the present invention, in reaction formula (c), the solvent is selected from one or more of DMF, PBS, water, DMSO, etc.; preferably, it is one or two of DMF, PBS, etc.

[0078] In the present invention, in reaction formula (c), the reaction temperature for the reaction of the glucosinolate compound to form the oxidized glucosinolate compound is 25-70°C; the reaction time is 8-16 hours; preferably, the reaction temperature is 25°C and the reaction time is 8 hours.

[0079] In the present invention, in reaction formula (c), the reaction temperature for the reaction of the oxidized glucosinolate compound and the ribonuclease A to generate the glucosinolate-labeled protein is 0-50°C; the reaction time is 1-16 hours; preferably, the reaction temperature is 25°C and the reaction time is 2 hours.

[0080] The present invention also provides a glucosinolate-labeled protein, the structural formula of which is shown in formula (10):

[0081]

[0082] in,

[0083] R is selected from benzyl, acyl, alkyl, and silicon; n is selected from an integer of 1 to 100;

[0084] Preferably, R is selected from benzyl, alkyl acyl, isopropyl, tert-butyldiphenylsilyl; n is selected from an integer of 1-10;

[0085] More preferably,

[0086] R is selected from benzyl, acetyl, isopropyl, tert-butyldiphenylsilyl; n is selected from an integer of 4-6.

[0087] Furthermore, the glucosinolate-labeled protein represented by formula (10) of the present invention comprises:

[0088]

[0089] In a specific embodiment, the synthesis reaction of the present invention is carried out in a reaction flask A, and 3-hydroxy-2-butanone (10 mmol) represented by formula (1), isopropylthiourea (10 mmol) represented by formula (2), and a first organic solvent (100 mL) are added to the reaction flask A, and the reaction system is stirred at 160° C. under a nitrogen atmosphere for 16 hours; after the reaction is completed, the mixture is cooled and filtered, the solid is dissolved in a second organic solvent (100 ml), liquid bromine (10 mmol) is added, and the reaction system is stirred at 25° C. under a nitrogen atmosphere for 3 hours; after the reaction is completed, the mixture is dried under reduced pressure, the residue is dissolved in a third organic solvent (100 ml), an alkenyl Grignard reagent (10 mmol) represented by formula (5) is added, the reaction system is stirred at 25° C. under a nitrogen atmosphere for 16 hours, and then NaSbF6 (30 mmol) is added; after the reaction is completed, silica gel is added and dried, and the target product, i.e., an imidazole alkenyl sulfide reagent represented by formula (6), is obtained by column chromatography.

[0090] In another specific embodiment, the synthesis reaction of the present invention is carried out in a reaction flask B, and a carbohydrate compound (0.2 mmol) represented by formula (7), an imidazole sulfide reagent (0.3 mmol) represented by formula (6), a base (1.4 mol), and an organic solvent (2 mL) are added to the reaction flask B, and the reaction system is stirred at 25° C. under an air atmosphere for 16 hours; after the reaction is completed, silica gel is added and dried, and the target product, i.e., a glucosidoglycoside compound represented by formula (8), is obtained by column chromatography.

[0091] In another specific embodiment, the synthesis reaction of the present invention is carried out in a reaction bottle C, and a glucosinolate compound (0.2 mmol) represented by formula (8), an oxidant (0.44 mmol), and an organic solvent (2 mL) are added to the reaction bottle C, and the reaction system is stirred at 25° C. under an air atmosphere for 8 hours; after the reaction is completed, silica gel is added and dried, and the target product is obtained by column chromatography separation; then, an oxidized glucosinolate compound (0.1 mmol) represented by formula (9), a protein (0.001 mmol), a photosensitizer (0.01 mmol), and a solvent (1 mL) are added to the reaction bottle D, and the reaction system is stirred at 25° C. under a nitrogen atmosphere for 2 hours; after the reaction is completed, a glucosinolate-labeled protein represented by formula (10) is obtained, and MALDI-MS detection is performed.

[0092] The present invention also provides an imidazolyl sulfide reagent compound as shown in formula (6) prepared according to the above-mentioned synthesis method of the present invention.

[0093] The present invention also proposes the use of the imidazolyl thioreductase compound represented by formula (6) in the preparation of glucosinolate compounds.

[0094] The present invention also proposes the use of the glucosinolate compound represented by formula (8) in the preparation of glucosinolate-labeled proteins.

[0095] The yields of the imidazolyl sulfide reagent compound represented by formula (6) and the glucosidoside compound represented by formula (8) prepared by the synthesis method of the present invention are 40% or more.

[0096] The present invention has the following advantages: no pre-functionalization of raw materials is required, no metal catalysis is required, raw materials are inexpensive and readily available, reaction substrates are easy to prepare, the reaction operation is simple, the reaction is efficient, and the yield is high. The imidazolyl sulfide reagent is simple to prepare, stable, and has no irritating odor; and the reaction conditions are relatively mild. The imidazolyl sulfide reagent of the present invention reacts with a carbohydrate compound to produce a glucosidic compound. The reaction operation is simple, the reaction conditions are relatively mild, and the compound can be used to construct a new type of glucosidic compound, making it suitable for large-scale industrial production. DETAILED DESCRIPTION

[0097] The present invention will be further described in detail with reference to the following specific examples, and the protection content of the present invention is not limited to the following examples. Without departing from the spirit and scope of the inventive concept, changes and advantages that can be thought of by those skilled in the art are included in the present invention, and the scope of protection is based on the appended claims. The process, conditions, reagents, experimental methods, etc. for implementing the present invention, except for the contents specifically mentioned below, are all common knowledge and common common sense in the art, and the present invention does not particularly limit the content.

[0098] Obviously, the described embodiments are only some of the embodiments of the present invention, rather than all of them. The following description of at least one exemplary embodiment is merely illustrative and is in no way intended to limit the present invention, its application, or use. All other embodiments derived by persons of ordinary skill in the art based on the embodiments of the present invention without inventive effort are intended to fall within the scope of protection of the present invention.

[0099] In all examples shown and discussed herein, any specific values ​​should be interpreted as merely exemplary and not limiting. Therefore, other examples of the exemplary embodiments may have different values.

[0100] The present invention discloses an imidazolylsulfur reagent, a synthesis method thereof, and an application thereof in the selective construction of glucosinolate compounds. The method comprises reacting a compound represented by formula (1) and isopropylthiourea represented by formula (2) in an organic solvent to obtain the imidazolylsulfur reagent; and reacting a saccharide compound represented by formula (7) and an imidazolylsulfur reagent represented by formula (6) in an organic solvent under the action of a base to obtain the glucosinolate compound. The present invention has mild reaction conditions, inexpensive and readily available raw materials, simple reaction operation, high yield and selectivity, and easy preparation of reaction substrates. The reaction of the present invention can be used to construct novel imidazolylsulfur reagents and glucosinolate compounds, and has broad application prospects and practical value.

[0101] The data given in the following examples include specific operation and reaction conditions and products. The purity of the products was determined by nuclear magnetic resonance.

[0102] The synthesis reaction of the imidazolyl sulfide reagent and the glucosinolate compound of the present invention comprises the following steps:

[0103] As shown in reaction formula (a), the synthesis reaction of the present invention is to add 3-hydroxy-2-butanone shown in formula (1), isopropylthiourea shown in formula (2), liquid bromine, an alkenyl Grignard reagent shown in formula (5), NaSbF6, and an organic solvent into a reaction flask A, and stir the reaction system at 0-160° C. under a nitrogen atmosphere for 16 hours; after the reaction is completed, silica gel is added and dried by spin drying, and the target product, i.e., an imidazole alkenyl sulfide reagent shown in formula (6), is obtained by column chromatography separation.

[0104] As shown in reaction formula (b), the synthesis reaction of the present invention is to add the carbohydrate compound represented by formula (7), the imidazole sulfide reagent represented by formula (6), a base, and an organic solvent into a reaction bottle B, and stir the reaction system at 25° C. in an air atmosphere for 16 hours; after the reaction is completed, silica gel is added and dried, and the target product, i.e., the glucosidic compound represented by formula (8), is obtained by column chromatography separation.

[0105] As shown in reaction formula (c), the synthetic reaction of the present invention is to add the glucosinolate compound shown in formula (8), an oxidant, and a solvent into a reaction flask C, and stir the reaction system at 25° C. in an air atmosphere for 8 hours; after the reaction is completed, add silica gel and spin-dry, and separate by column chromatography to obtain the target product; then, add the oxidized glucosinolate compound shown in formula (9), a protein, a photosensitizer, and a solvent into a reaction flask D, and stir the reaction system at 25° C. in a nitrogen atmosphere for 2 hours; after the reaction is completed, a glucosinolate-labeled protein shown in formula (10) is obtained, and MALDI-MS detection is performed.

[0106] The imidazolyl sulfide reagents shown in Table 1 are all products synthesized by the method of the present invention. There is no public document that discloses these compounds.

[0107] Table 1 New imidazolyl sulfide reagents of the present invention

[0108]

[0109] The glucosinolate compounds shown in Table 2 are all products synthesized by the method of the present invention, and no public literature has disclosed these compounds.

[0110] Table 2 New glucosinolate compounds of the present invention

[0111]

[0112]

[0113] The oxidized glucosinolate compounds shown in Table 3 are all products synthesized by the method of the present invention, and no public literature has disclosed these compounds.

[0114] Table 3 New oxidized glucosinolate compounds of the present invention

[0115]

[0116]

[0117] The glucosinolate-labeled proteins shown in Table 4 are all products synthesized by the method of the present invention. There is no public literature that discloses these compounds.

[0118] Table 4 New glucosinolate-labeled proteins of the present invention

[0119]

[0120] Example 1

[0121] Synthesis of compound 6a:

[0122]

[0123] To a reaction tube, imidazolium bromide (372.16 mg, 1 mmol, 1 equiv), vinyl Grignard reagent (10 mL, 1 mmol, 1 equiv), NaSbF6 (776.22 mg, 3 mmol, 3 equiv), and THF (tetrahydrofuran) (10 mL) were added and reacted at 25°C for 16 hours. After completion, the reaction was dried and column chromatography afforded a brown solid 6a (389.62 mg, 82%). 1 H NMR (400MHz, CDCl3) δ6.39–6.31(m,1H),5.21–5.11(m,1H),5.10–5.01(m,2H) ,4.96(d,J=11.0Hz,1H),2.81(s,3H),2.79(s,3H),1.69(s,6H),1.62(s,6H). 13 C NMR (101MHz, CDCl3) δ142.1,138.8,137.8,132.3,115.2,52.1,47.5,27.1,22.3,11.2,10.2IR(neat,cm -1 )3102,1684,1498,1479,1359,1238,1136,1060,1039,694.HRMS(ESI)m / z:[M] + Calcd for C 13 H 23 N2S239.4005,Found239.4001.

[0124] Example 2

[0125] Synthesis of compound 6b:

[0126]

[0127] To a reaction tube, imidazolium bromide (372.16 mg, 1 mmol, 1 equiv), isopropenyl Grignard reagent (10 mL, 1 mmol, 1 equiv), NaSbF6 (776.22 mg, 3 mmol, 3 equiv), and THF (tetrahydrofuran) (10 mL) were added and reacted at 25°C for 16 hours. After completion of the reaction, the mixture was evaporated to dryness and column chromatography was performed to afford 6b (415.80 mg, 85%) as a white solid.1 H NMR (400MHz, CDCl3) δ5.20–5.10(m,1H),5.08–5.02(m,2H),2.87(s,3H),2.42(s,3H),2.02(s,3H),1.69(s,6H),1.62(s,6H). 13 C NMR (101MHz, CDCl3) δ142.1,138.8,137.8,132.3,115.2,52.1,47.5,27.1,23.5,22.3,11.2,10.2IR(neat,cm -1 )3102,1684,1498,1479,1359,1238,1136,1060,1039,694.HRMS(ESI)m / z:[M] + Calcd for C 14 H 25 N2S253.4275,Found 253.4269.

[0128] Example 3

[0129] Synthesis of compound 6c:

[0130]

[0131] To a reaction tube, imidazolium bromide (372.16 mg, 1 mmol, 1 equiv), cyclohexyl Grignard reagent (10 mL, 1 mmol, 1 equiv), NaSbF6 (776.22 mg, 3 mmol, 3 equiv), and THF (tetrahydrofuran) (10 mL) were added and reacted at 25°C for 16 hours. After completion, the reaction was dried and column chromatography afforded compound 6c (486.90 mg, 92%) as a white solid. 1 H NMR (400MHz, CDCl3) δ5.30–5.25(m,1H),2.91(s,3H),2.00-1.94(m,4H),1.76-1.74(m,2H),1.69(s,6H),1.62(s,6H),1.66-1.61(m,2H). 13 C NMR (101MHz, CDCl3) δ147.1,142.4,136.6,134.9,124.9,52.1,47.0,26.2,24.3,22.5,22.3,11.2,9.4IR(neat,cm -1 )3102,1684,1498,1479,1359,1238,1136,1060,1039,694.HRMS(ESI)m / z:[M] +Calcd for C 17 H 29 N2S293.4925,Found293.4919.

[0132] Example 4

[0133] Synthesis of compound 6d:

[0134]

[0135] To a reaction tube, imidazolium bromide (372.16 mg, 1 mmol, 1 equiv), cycloheptenyl Grignard reagent (10 mL, 1 mmol, 1 equiv), NaSbF6 (776.22 mg, 3 mmol, 3 equiv), and THF (tetrahydrofuran) (10 mL) were added and reacted at 25°C for 16 hours. After completion of the reaction, the mixture was spin-dried and column chromatography yielded compound 6d (483.51 mg, 89%) as a white solid. 1 H NMR (400MHz, CDCl3) δ5.30–5.25(m,1H),2.91(s,3H),2.00-1.94(m,4H),1.76 -1.74(m,2H),1.69(s,6H),1.62(s,6H),1.66-1.61(m,2H),1.53-1.50(m,2H). 13 C NMR (101MHz, CDCl3) δ147.1,142.4,136.6,134.9,114.2,52.1,47.0,31.6,26.2,24.3,22.5,22.3,11.2,9.4IR(neat,cm -1 )3102,1684,1498,1479,1359,1238,1136,1060,1039,694.HRMS(ESI)m / z:[M] + Calcd for C 18 H 31 N2S 307.5195,Found 307.5192.

[0136] Example 5

[0137] Synthesis of compound 6e:

[0138]

[0139] To a reaction tube, imidazolium bromide (372.16 mg, 1 mmol, 1 equiv), sterol Grignard reagent (10 mL, 1 mmol, 1 equiv), NaSbF6 (776.22 mg, 3 mmol, 3 equiv), and THF (tetrahydrofuran) (10 mL) were added and reacted at 25°C for 16 hours. After completion of the reaction, the mixture was evaporated to dryness and column chromatography was performed to afford 6e (675.37 mg, 81%) as a white solid. 1 H NMR (400MHz, CDCl3) δ5.72(dd,J=3.0,1.6Hz,1H),5.35(dd,J=3.3,1.8Hz,1H),4.93(dd,J=10.5,2.8Hz,2H),4.88–4.83(m,2H),4.77(d,J=10 .2Hz,1H),4.67(d,J=9.8Hz,1H),4.59(m,3H),3.79(dd,J=10.9,1.7Hz,1H),3.71(d,J=9.0Hz,1H),3.68–3.60(m,2H),3.52(m,2H),2.29(dd,J =17.8,6.7Hz,1H),2.23–2.19(m,1H),2.15(m,1H),2.05–1.99(m,1H), 1.96(m,1H),1.89–1.85(m,1H),1.81(dt,J=13.2,3.3Hz,1H),1.74(d,J =13.4Hz,1H),1.69(dd,J=10.7,4.6Hz,1H),1.67–1.61(m,3H),1.56(m ,3H),1.46(m,2H),1.04(s,3H),0.94(s,3H),0.91(s,9H),0.08(s,6H). 13 C NMR (126MHz, CDCl3) δ146.2,141.9,138.5,138.3,138.1,138.0,128.5,128. 4,128.3,127.9,127.8,127.6,127.5,125.1,120.8,86.8,85.2,81.1,79.3,7 7.9,75.9,75.6,75.1,73.3,72.6,69.0,56.5,50.6,48.7,42.9,37.3,36.8, 34.6,32.1,31.5,30.6,30.2,26.0,20.8,19.4,18.3,16.3,-4.5.IR(neat,cm -1 )2882,1686,1498,1472,1368,1238,1136,1064,1039,694.HRMS(ESI)m / z:[M]+ Calcd for C 36 H 61 N2SSiO 598.0415,Found 598.0411.

[0140] Example 6

[0141] Synthesis of compound 8a:

[0142]

[0143] A saccharide (108 mg, 0.2 mmol, 1 equiv), an imidazolyl sulfide reagent (142.6 mg, 0.3 mmol, 1.5 equiv), CsOH·H2O (235 mg, 1.4 mmol, 7 equiv), and acetone (2 mL) were added to a reaction tube and reacted at 25°C for 16 hours. After completion of the reaction, the mixture was spin-dried and purified by column chromatography to afford 8a (99.1 mg, 85%) as a white solid. 1 H NMR (400MHz, CDCl3) δ7.39–7.31(m,18H),7.21(dd,J=7.1,2.3Hz,2H),6.59(dd,J=16.9,9.9Hz,1H),5.44(dd,J=33.9,13.4Hz,2H),4.96(d ,J=11.0Hz,1H),4.91(t,J=10.6Hz,2H),4.86(d,J=10.8Hz,1H),4.79(d,J=10.3Hz,1H),4.68–4.56(m,4H),3.81–3.67(m,4H),3.56(m,2H). 13 CNMR (101MHz, CDCl3) δ138.5,138.2,138.0,137.9,129.1,128.5,128.4,128.0,127.9,127 .8,127.8,127.7,115.9,84.7,81.2,79.5,77.8,75.8,75.5,75.1,73.5,68.9.IR(neat,cm -1 )3102,1684,1498,1479,1359,1238,1136,1060,1039,694.HRMS(ESI)m / z:[M+Na] + Calcd for C 36 H 38 O5SNa 605.2338,Found 605.2326.Mp:64.5–65.1℃.

[0144] Example 7

[0145] Synthesis of compound 8b:

[0146]

[0147] A carbohydrate compound (108 mg, 0.2 mmol, 1 equiv), an imidazolyl sulfide reagent (146.8 mg, 0.3 mmol, 1.5 equiv), CsOH·H2O (235 mg, 1.4 mmol, 7 equiv), and acetone (2 mL) were added to a reaction tube and reacted at 25°C for 16 hours. After completion of the reaction, the mixture was spin-dried and column chromatography afforded the compound 8b (66.8 mg, 56%) as a colorless liquid. 1 H NMR (400MHz, CDCl3) δ7.45–7.41(m,2H),7.39–7.31(m,16H),7.25–7.18(m,2H),5.25–5.17(m,2H),4.96(dd,J=15.0,11.4 Hz,3H),4.91–4.85(m,1H),4.79(dd,J=11.9,10.2Hz,2H),4.62(m,3H),3.84–3.66(m,4H),3.63–3.53(m,2H),2.11(s,3H). 13 C NMR (101MHz, CDCl3) δ138.9,138.5,138.3,138.1,138.0,128.5,128.4,128.3,128.0,127.9,12 7.8,127.6,112.6,86.8,84.8,81.1,79.2,77.9,75.9,75.6,75.1,73.5,69.0,24.2.IR(neat,cm -1 )3108,1692,1496,1479,1359,1238,1136,1060,1039,694.HRMS(EI)m / z:[M+Na] + Calcd for C 37 H 40 O5SNa619.2494,Found619.2486.

[0148] Example 8

[0149] Synthesis of compound 8c:

[0150]

[0151] A carbohydrate compound (108 mg, 0.2 mmol, 1 equiv), an imidazolyl sulfide reagent (158.8 mg, 0.3 mmol, 1.5 equiv), CsOH·H2O (235 mg, 1.4 mmol, 7 equiv), and acetone (2 mL) were added to a reaction tube and reacted at 25°C for 16 hours. After completion of the reaction, the mixture was spin-dried and purified by column chromatography to afford 8c (79.0 mg, 62%) as a white solid. 1 H NMR (500MHz, CDCl3) δ7.42–7.38(m,2H),7.36–7.27(m,16H),7.21(dd,J=7.5,1.8Hz,2H ),6.08–6.02(m,1H),4.93(dd,J=10.6,2.9Hz,2H),4.89–4.82(m,2H),4.76(d,J=10.2H z,1H),4.59(m,4H),3.78(dd,J=10.8,1.7Hz,1H),3.70(m,2H),3.63(t,J=9.4Hz,1H),3 .53–3.48(m,2H),2.39–2.22(m,2H),2.09(m,2H),1.71–1.64(m,2H),1.63–1.54(m,2H). 13 C NMR (126MHz, CDCl3) δ138.5,138.4,138.1,130.8,129.6,128.5,128.4,128.3,128.0,127.9,127.8,127.7,1 27.6,127.5,86.9,85.5,81.3,79.2,78.0,75.9,75.5,75.1,73.4,69.2,31.1,26.7,23.5,21.7.IR(neat,cm -1 )2860,1688,1498,1479,1359,1238,1136,1060,1039,694.HRMS(ESI)m / z:[M+Na] + Calcd for C 40 H 44 O5SNa 659.2807,Found 659.2789.Mp:81.9–83.1℃.

[0152] Example 9

[0153] Synthesis of compound 8d:

[0154]

[0155] A carbohydrate compound (108 mg, 0.2 mmol, 1 equiv), an imidazolyl sulfide reagent (163.0 mg, 0.3 mmol, 1.5 equiv), CsOH·H2O (235 mg, 1.4 mmol, 7 equiv), and acetone (2 mL) were added to a reaction tube and allowed to react at 25°C for 16 hours. After completion of the reaction, the mixture was spin-dried and column chromatography afforded 8d (87.2 mg, 67%) as a colorless liquid. 1 H NMR (400MHz, CDCl3) δ7.39(dd,J=7.9,1.4Hz,2H),7.35–7.27(m,16H),7.22–7.17(m,2H),6.18(t,J=6. 7Hz,1H),4.93(dd,J=10.5,2.1Hz,2H),4.85(dd,J=10.8,8.9Hz,2H),4.75(d,J=10.2Hz,1H),4.63–4.53 (m,4H),3.79–3.66(m,3H),3.62(t,J=9.3Hz,1H),3.55–3.46(m,2H),2.49(dd,J=7.1,3.7Hz,2H),2.15 (dd,J=11.4,6.3Hz,2H),1.72(dd,J=12.6,6.5Hz,2H),1.56(dd,J=12.3,5.8Hz,2H),1.51–1.44(m,2H). 13 C NMR (101MHz, CDCl3) δ138.5,138.3,138.1,136.4,133.1,128.5,128.4,128.3,127.9,127.8,127.7,127 .5,86.9,86.0,81.3,79.2,78.0,75.8,75.5,75.0,73.4,69.1,35.8,32.1,29.3,26.7,26.5.IR(neat,cm -1 )2864,1686,1498,1479,1359,1238,1136,1062,1039,694.HRMS(ESI)m / z:[M+Na] + Calcd for C 41 H 46 O5SNa 673.2964,Found 673.2950.

[0156] Example 10

[0157] Synthesis of compound 8e:

[0158]

[0159] A carbohydrate compound (108 mg, 0.2 mmol, 1 equiv), an imidazolyl sulfide reagent (142.6 mg, 0.3 mmol, 1.5 equiv), CsOH·H2O (235 mg, 1.4 mmol, 7 equiv), and acetone (2 mL) were added to a reaction tube and reacted at 25°C for 16 hours. After completion of the reaction, the mixture was spin-dried and column chromatography afforded the compound 8e (65.3 mg, 56%) as a colorless liquid. 1 H NMR(400MHz, CDCl3)δ7.40–7.27(m,20H),6.55(dd,J=16.9,10.0Hz,1H),5.37( dd,J=42.1,13.5Hz,2H),4.98(d,J=11.6Hz,1H),4.83(q,J=10.2Hz,2H),4.78–4 .70(m,2H),4.62(d,J=11.7Hz,1H),4.52(d,J=9.6Hz,1H),4.45(q,J=11.8Hz,2H ),3.99(d,J=2.7Hz,1H),3.95(t,J=9.4Hz,1H),3.62(s,3H),3.61–3.58(m,1H). 13 C NMR (101MHz, CDCl3) δ138.8,138.3,138.2,137.8,129.3,128.5,128.4,128.2,128.0,127.9,127 .8,127.7,127.6,127.5,115.3,85.0,84.0,77.8,77.5,75.8,74.5,73.6,72.7,68.5.IR(neat,cm -1 )3108,1686,1498,1359,1237,1138,1062,1039,694.HRMS(ESI)m / z:[M+Na] + Calcd for C 36 H 38 O5SNa 605.2338,Found605.2324.

[0160] Example 11

[0161] Synthesis of compound 8f:

[0162]

[0163] A carbohydrate compound (52 mg, 0.2 mmol, 1 equiv), an imidazolyl sulfide reagent (142.6 mg, 0.3 mmol, 1.5 equiv), CsOH·H2O (235 mg, 1.4 mmol, 7 equiv), and acetone (2 mL) were added to a reaction tube and reacted at 25°C for 16 hours. After completion, the reaction was evaporated to dryness and column chromatography afforded 8f (31.4 mg, 52%) as a colorless liquid. 1 H NMR(500MHz, CDCl3)δ6.36(dd,J=16.9,9.9,Hz,1H),5.51(s,1H),5.44–5.29(m,2H),4.79(dd,J=5.9,3.6Hz,1H),4.63(d, J=6.0Hz,1H),4.45(m,1H),4.10(dd,J=8.7,6.3Hz,1H),3.82(m,2H),1.49(s,3H),1.45(s,3H),1.38(s,3H),1.33(s,3H). 13 C NMR (126MHz, CDCl3) δ128.9,116.2,115.8,89.2,85.6,81.6,80.4,79.8,76.2,74.7,67.1,62.6,61.8,26.9,26.0,25.2,24.7.IR(neat,cm -1 )3106,1689,1498,1482,1359,1238,1136,1064,1039,889,694.HRMS(ESI)m / z:[M+Na] + Calcd for C 14 H 22 O5SNa 325.1086,Found 325.1071.

[0164] Example 12

[0165] Synthesis of compound 8g:

[0166]

[0167] A carbohydrate compound (84 mg, 0.2 mmol, 1 equiv), an imidazolyl sulfide reagent (142.6 mg, 0.3 mmol, 1.5 equiv), CsOH·H2O (235 mg, 1.4 mmol, 7 equiv), and acetone (2 mL) were added to a reaction tube and allowed to react at 25°C for 16 hours. After the reaction was complete, the mixture was dried and column chromatography yielded 8 g (56.4 mg, 61%) of a colorless liquid. 1H NMR (400MHz, CDCl3) δ7.40–7.28(m,15H),6.50(dd,J=16.9,9.9Hz,1H),6.37(dd,J=16.9,10.0Hz,1H),5.40(dd,J=25.5,13.4Hz,2H),4.95–4.83 (m,3H),4.80–4.71(m,2H),4.65(d,J=11.7Hz,1H),4.56(d,J=9.3Hz,1H ),4.10–4.03(m,1H),3.68–3.62(m,2H),3.47(m,1H),3.33–3.26(m,1H). 13 C NMR (101MHz, CDCl3) δ138.5,138.0,137.9,129.0,128.5,128.4,128.8,128.1,128. 0,127.9,127.8,116.1,85.3,85.2,80.5,77.7,75.7,75.5,73.3,67.7.IR(neat,cm -1 )3104,1686,1498,1479,1359,1231,1137,1060,1039,694.HRMS(ESI)m / z:[M+Na] + Calcd for C 28 H 30 O4SNa485.1762,Found 485.1746.

[0168] Example 13

[0169] Synthesis of compound 8h:

[0170]

[0171] A carbohydrate compound (84 mg, 0.2 mmol, 1 equiv), an imidazolyl sulfide reagent (142.6 mg, 0.3 mmol, 1.5 equiv), CsOH·H2O (235 mg, 1.4 mmol, 7 equiv), and acetone (2 mL) were added to a reaction tube and allowed to react at 25°C for 16 hours. After the reaction was complete, the mixture was dried and column chromatography afforded 8h (49.0 mg, 53%) as a colorless liquid. 1H NMR (500MHz, CDCl3) δ7.39 (d, J = 6.9 Hz, 2H), 7.35–7.29 (m, 11H), 7.25–7.22 (m, 2H), 6.54 (dd, J = 16.9, 10. 0Hz,1H),5.69(d,J=5.5Hz,1H),5.40(d,J=16.9Hz,1H),5.29(d,J=10.0Hz,1H),4.74(d,J=11.8Hz,1H),4. 70(d,J=12.1Hz,1H),4.63(d,J=11.8Hz,1H),4.52(t,J=11.5Hz,2H),4.44(d,J=12.1Hz,1H),4.32(m,1H) ,4.18(t,J=5.6Hz,1H),3.98(t,J=5.5Hz,1H),3.61(dd,J=10.9,3.2Hz,1H),3.51(dd,J=10.9,3.4Hz,1H). 13 C NMR (126MHz, CDCl3) δ138.0,137.6,131.5,128.4,128.3,127.9,127.8,127.7,114.1,88.3,81.0,78.2,73.5,73.2,72.6,69.1.IR(neat,cm -1 )3106,1680,1492,1479,1359,1238,1136,1060,1039,694.HRMS(ESI)m / z:[M+H] + Calcd for C 28 H 31 O4S 463.1943,Found 463.1932.

[0172] Example 14

[0173] Synthesis of compound 8i:

[0174]

[0175] A carbohydrate compound (52 mg, 0.2 mmol, 1 equiv), an imidazolyl sulfide reagent (142.6 mg, 0.3 mmol, 1.5 equiv), CsOH·H2O (235 mg, 1.4 mmol, 7 equiv), and acetone (2 mL) were added to a reaction tube and allowed to react at 25°C for 16 hours. After completion of the reaction, the mixture was spin-dried and column chromatography afforded 8i (37.5 mg, 62%) as a colorless liquid. 1H NMR (400MHz, CDCl3) δ6.36(dd,J=16.9,10.0Hz,1H),5.51(s,1H),5.35(dd,J=18.8,13.4Hz,2H),4.78(dd,J=5.9,3.6Hz,1H),4.63(d,J=6.0Hz,1H),4 .45(m,1H),4.10(dd,J=8.7,6.3Hz,1H),4.05(dd,J=8.0,3.5Hz,1H),3.99( dd,J=8.7,4.3Hz,1H),1.49(s,3H),1.45(s,3H),1.38(s,3H),1.33(s,3H). 13 C NMR (101MHz, CDCl3) δ129.0,115.8,113.1,109.4,89.2,85.6,80.4,79.8,72.7,67.1,26.9,26.0,25.2,24.7.IR(neat,cm -1 )3110,1688,1498,1479,1359,1238,1136,1060,1039,694.HRMS(ESI)m / z:[M+Na] + Calcd for C 14 H 22 O5SNa 325.1086,Found 325.1078.

[0176] Example 15

[0177] Synthesis of compound 8j:

[0178]

[0179] A carbohydrate compound (194.6 mg, 0.2 mmol, 1 equiv), an imidazolyl sulfide reagent (142.6 mg, 0.3 mmol, 1.5 equiv), CsOH·H2O (235 mg, 1.4 mmol, 7 equiv), and acetone (2 mL) were added to a reaction tube and allowed to react at 25°C for 16 hours. After completion of the reaction, the mixture was spin-dried and column chromatography afforded 8j (123.8 mg, 61%) as a colorless liquid. 1H NMR (400MHz, CDCl3) δ7.35–7.18(m,33H),7.10(m,2H),6.48(dd,J=16.9,9.9Hz,1H),5.35(dd ,J=34.3,13.4Hz,2H),5.07(d,J=10.5Hz,1H),4.94(d,J=11.4Hz,1H),4.76m,3H),4.68(m,3H) ,4.55–4.46(m,3H),4.44–4.30(m,4H),4.22(d,J=11.8Hz,1H),3.96(t,J=9.4Hz,1H),3.89(d ,J=2.7Hz,1H),3.76(m,3H),3.57(t,J=8.9Hz,1H),3.46(dd,J=18.6,9.3Hz,2H),3.37(m,4H). 13 C NMR (101MHz, CDCl3) δ139.1,139.0,138.8,138.5,138.4,138.1,129.0,128.4,128.3,128.2,128.0,127.9,127.8,127.7,127.6,127.5, 127.4,127.2,115.8,102.7,84.8,84.6,82.6,80.5,80.0,79.7,77.2,76.3,75.6,75.4,74.7,73.7,73.4,73.1,72.6,68.1.IR(neat,cm -1 )3106,1688,1498,1479,1359,1238,1137,1066,1039,694.HRMS(ESI)m / z:[M+Na] + Calcd for C 63 H 66 O 10 SNa 1037.4274, Found 1037.4275.

[0180] Example 16

[0181] Synthesis of compound 8k:

[0182]

[0183] A carbohydrate compound (281 mg, 0.2 mmol, 1 equiv), an imidazolyl sulfide reagent (142.6 mg, 0.3 mmol, 1.5 equiv), CsOH·H2O (235 mg, 1.4 mmol, 7 equiv), and acetone (2 mL) were added to a reaction tube and allowed to react at 25°C for 16 hours. After completion of the reaction, the mixture was spin-dried and column chromatography yielded 8k (240.3 mg, 83%) as a colorless liquid. 1 H NMR(500MHz, CDCl3)δ7.42(d,J=7.3Hz,2H),7.38–7.35(m,4H),7.34(dd,J=3.6,2.5H z,4H),7.32–7.27(m,31H),7.23(m,9H),6.38(dd,J=16.9,9.9Hz,1H),5.35(d,J=16.9 Hz,1H),5.19(d,J=9.9Hz,1H),5.10(d,J=3.5Hz,1H),4.94(dd,J=11.4,8.2Hz,2H),4. 86(s,1H),4.84(t,J=4.9Hz,2H),4.81–4.77(m,6H),4.74(d,J=11.8Hz,1H),4.69(s,1 H),4.66(d,J=3.6Hz,1H),4.63(d,J=2.0Hz,1H),4.61–4.56(m,3H),4.55(d,J=2.0Hz ,1H),4.52(d,J=5.5Hz,1H),4.50–4.45(m,2H),4.41(d,J=11.7Hz,1H),4.06–4.00(m, 5H),3.99–3.93(m,4H),3.79(d,J=3.1Hz,1H),3.75(dd,J=9.7,5.6Hz,1H),3.69(t,J= 9.4Hz,1H),3.62(d,J=8.9Hz,1H),3.58–3.55(m,2H),3.42(m,1H),3.24–3.17(m,1H). 13C NMR (126MHz, CDCl3) δ138.9,138.8,138.7,138.3,138.0,137.9,129.2,128.5,128.4,1 28.3,128.2,128.1,128.0,127.9,127.8,127.7,127.6,127.5,127.4,127.3,115.5,98. 0,97.8,83.4,84.5,81.1,79.3,79.2,78.2,77.7,77.3,76.6,76.4,75.5,75.4,75.3,7 5.0,74.9,74.8,73.5,72.8,72.7,72.6,69.4,69.0,68.9,66.5,65.5,60.4.IR(neat,cm -1 )3103,1685,1488,1472,1359,1238,1138,1060,1039,694.HRMS(ESI)m / z:[M+Na] + Calcd for C 90 H 94 O 15 SNa 1469.6211, Found 1469.6209.

[0184] Example 17

[0185] Synthesis of compound 81:

[0186]

[0187] A carbohydrate compound (108 mg, 0.2 mmol, 1 equiv), an imidazolyl sulfide reagent (250.1 mg, 0.3 mmol, 1.5 equiv), CsOH·H2O (235 mg, 1.4 mmol, 7 equiv), and acetone (2 mL) were added to a reaction tube and allowed to react at 25°C for 16 hours. After completion of the reaction, the mixture was spin-dried and column chromatography yielded 81 (118.5 mg, 62%) as a colorless liquid. 11H NMR (500 MHz, CDCl3) δ 7.41–7.38 (m, 2H), 7.34–7.28 (m, 16H), 7.22–7.19 (m, 2H), 5.72 (dd, J = 3.0, 1.6 Hz, 1H), 5.35 (dd, J = 3.3, 1.8 Hz, 1H), 4.93 (dd, J = 10.5, 2.8 Hz, 2H), 4.88–4.83 (m, 2H), 4.77 (d, J = 10.2 Hz, 1H), 4.67 (d, J = 9.8 Hz, 1H), 4.59 (m, 3H), 3.79 (dd, J = 10.9, 1.7 Hz, 1H), 3.71 (d, J = 9.0 Hz, 1H), 3.68–3.60 (m, 2H), 3.52 (m, 2H), 2.29 (dd, J = 17.8, 6.7 Hz, 1H), 2.23–2.19 (m, 1H), 2.15 (m, 1H), 2.05–1.99 (m, 1H), 1.96 (m,​​​​​​​​​​​​​

[0189] Synthesis of compound 9a:

[0190]

[0191] A glucosinolate (101.5 mg, 0.1 mmol, 1 equiv), m-CPBA (61 mg, 0.25 mmol, 2.5 equiv), and chloroform (1 mL) were added to a reaction tube and reacted at 25°C for 8 hours. After the reaction was complete, the mixture was dried and column chromatography afforded the colorless liquid 9a (97.4 mg, 93%). 1 H NMR (500MHz, CDCl3) δ7.38–7.23(m,33H),7.16(t,J=7.3Hz,2H),6.70(dd,J=16.7,9.9Hz,1 H),6.47(d,J=16.8Hz,1H),6.11(d,J=9.9Hz,1H),5.14(d,J=10.6Hz,1H),4.98(d,J=11.4Hz ,1H),4.93–4.87(m,2H),4.85(d,J=11.1Hz,1H),4.73(dd,J=17.9,11.1Hz,4H),4.57(d,J=1 1.4Hz,1H),4.48(dd,J=17.3,9.9Hz,2H),4.42–4.30(m,3H),4.27(d,J=11.8Hz,1H),4.00(m 2H), 3.94 (d, J=2.6Hz, 1H), 3.80 (m 2H), 3.72 (dd, J=14.0, 5.0Hz, 2H), 3.44 (m, 5H). 13 C NMR (126MHz, CDCl3) δ169.2,139.0,138.7,138.7,138.5,138.2,138.1,137.7,1 35.0,133.7,131.2,130.3,129.9,128.6,128.5,128.4,128.3,128.2,128.1,12 7.9,127.8,127.6,127.5,127.4,127.3,102.9,91.2,84.4,82.6,80.1,79.9,76 .7,75.8,75.6,75.4,74.8,73.6,73.5,73.2,73.1,72.6,68.1,67.8.IR(neat,cm -1 )3528,3102,1686,1496,1478,1359,1236,1134,1062,1039,694.HRMS(ESI)m / z:[M+Na] +Calcd for C 63 H 66 O 12 SNa 1069.4173, Found 1069.4162.

[0192] Example 19

[0193] Synthesis of compound 9b:

[0194]

[0195] A glucosinolate compound (144.7 mg, 0.1 mmol, 1 equiv), m-CPBA (61 mg, 0.25 mmol, 2.5 equiv), and chloroform (1 mL) were added to a reaction tube and reacted at 25°C for 8 hours. After the reaction was complete, the mixture was dried and column chromatography afforded a colorless liquid 9b (134.7 mg, 91%). 1 H NMR (500MHz, CDCl3) δ7.40–7.25(m,50H),6.68(dd,J=16.7,9.9Hz,1H),6.39(d,J=16.7Hz,1H),5.92(d,J=9.9Hz,1H),5.08(d,J=3.4H z,1H),5.00(dd,J=11.3,8.4Hz,2H),4.92–4.88(m,4H),4.87–4.84(m,3H),4.81(dd,J=8.7,4.6Hz,3H),4.76(dd,J=16.3,8.3Hz,2H), 4.71–4.66(m,2H),4.62(d,J=11.2Hz,3H),4.55(d,J=11.8Hz,1H),4.47(d,J=11.7Hz,1H),4.28(d,J=9.5Hz,1H),4.15–4.10(m,2H),4 .09–3.95(m,7H),3.88(t,J=8.9Hz,1H),3.84–3.77(m,3H),3.74(dd,J=16.4,8.7Hz,2H),3.64(t,J=8.5Hz,3H),3.50(d,J=5.2Hz,1H). 13C NMR (126MHz, CDCl3) δ169.5,138.8,138.7,138.4,138.1,137.8,137.5,135.2,134.7,133.7 ,131.4,131.3,130.3,129.9,128.7,128.5,128.4,128.3,128.2,128.0,127.9,127.8,127. 7,127.6,127.5,127.4,98.3,97.5,90.9,86.1,80.3,79.3,78.1,77.3,77.1,76.6,76.4,75 .8,75.5,75.2,74.9,74.8,73.7,73.5,72.9,72.8,72.7,69.7,69.2,66.6,64.9.IR(neat,cm -1 )3526,3101,1675,1486,1472,1358,1236,1134,1064,1052,693.HRMS(ESI)m / z:[M+Na] + Calcd for C 90 H 94 O17SNa 1501.6109,Found 1501.6102.

[0196] Example 20

[0197] Synthesis of compound 10a:

[0198]

[0199] To a reaction flask, an oxidized glucosinolate compound (104.7 mg, 0.1 mmol, 100 equiv), RNase A (5 mg, 0.001 mmol, 1 equiv), a photosensitizer (10.5 mg, 0.01 mmol, 10 equiv), and a solvent (1 mL) were added. The reaction system was stirred at 25°C under a nitrogen atmosphere for 2 hours. After completion of the reaction, 10a was obtained, which was detected by MALDI-MS. MALDI-MS: 14747.5000.

[0200] Example 21

[0201] Synthesis of compound 10b:

[0202]

[0203] To a reaction flask, an oxidized glucosinolate compound (147.9 mg, 0.1 mmol, 100 equiv), RNase A (5 mg, 0.001 mmol, 1 equiv), a photosensitizer (10.5 mg, 0.01 mmol, 10 equiv), and a solvent (1 mL) were added. The reaction system was stirred at 25°C under a nitrogen atmosphere for 2 hours. After completion of the reaction, 10b was obtained, which was detected by MALDI-MS. MALDI-MS: 15178.6213.

[0204] Unless otherwise defined, all technical and scientific terms used in the present invention have the same meaning as those commonly understood by those skilled in the art of the present invention. The terms used in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention.

[0205] As used in the present invention, the term "comprising" is an open expression, that is, including the contents specified in the present invention, but not excluding other aspects.

[0206] As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items.

[0207] The protection content of the present invention is not limited to the above embodiments. Without departing from the spirit and scope of the inventive concept, changes and advantages that can be thought of by those skilled in the art are included in the present invention and are protected by the appended claims.

Claims

1. An imidazolyl sulfide reagent, characterized in that The structure of the imidazolyl sulfide reagent is shown in formula (6): Among them, R 1 is selected from alkenyl and substituted alkenyl; wherein the substituted alkenyl is selected from alkyl substituted alkenyl.

2. A method for synthesizing an imidazolyl sulfide reagent, characterized in that: 3-Hydroxy-2-butanone represented by formula (1) and isopropylthiourea represented by formula (2) are used as reaction raw materials, and react in an organic solvent to obtain an imidazolyl sulfide reagent represented by formula (6). The reaction process is shown in reaction formula (a); Among them, R 1 is selected from alkenyl and substituted alkenyl; wherein the substituted alkenyl is selected from alkyl substituted alkenyl.

3. The synthesis method according to claim 2, wherein The amount ratio of the 3-hydroxy-2-butanone represented by formula (1), the isopropylthiourea represented by formula (2) and the first organic solvent is 1 mol: (1-3) mol: (5-10) volume; the amount ratio of the imidazole thiourea represented by formula (3) and liquid bromine to the second organic solvent is 1 mol: (1-3) mol: (5-10) volume; the amount ratio of the bromoimidazole sulfonate represented by formula (4), the alkenyl Grignard reagent represented by formula (5), NaSbF6 and the third organic solvent is 1 mol: (1-3) mol: (1-5) mol: (5-10) volume; and / or the first organic solvent, the second organic solvent and the third organic solvent are all selected from one or more of n-hexanol, dichloromethane and tetrahydrofuran.

4. The synthesis method according to claim 2, wherein The reaction temperature of the 3-hydroxy-2-butanone and the isopropylthiourea to generate the imidazolethiourea is 0-160° C.; the reaction time is 3-16 hours; and / or, The reaction temperature of the imidazole thiourea and the liquid bromine to generate the brominated imidazole thiosalt is 0°C to room temperature; The reaction time is 1-6 hours; and / or, The reaction temperature for the reaction of the bromoimidazole sulfonate, the alkenyl Grignard reagent and NaSbF6 to generate the imidazolyl alkenyl sulfide reagent is 0°C to room temperature; and the reaction time is 1-16 hours.

5. Use of an imidazolyl thioreductase in the selective construction of glucosinolate compounds, characterized in that: The saccharide compound represented by formula (7) and the imidazolyl sulfide reagent represented by formula (6) are used as reaction raw materials. Under the action of a base, in an organic solvent, a glucosidic compound represented by formula (8) is reacted. The reaction process is shown in reaction formula (b): in, R is selected from benzyl, acyl, alkyl, and silicon; R 1 is selected from alkenyl and substituted alkenyl; wherein the substituted alkenyl is selected from alkyl substituted alkenyl; and n is selected from an integer of 4-6.

6. The use according to claim 5, characterized in that The base is selected from one or more of sodium carbonate, potassium carbonate, cesium carbonate, potassium tert-butoxide, lithium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide monohydrate, pyridine, 2,6-lutidine, 2,4,6-trimethylpyridine, triethylamine, diisopropylethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, tetramethylguanidine, 2-tert-butyl-1,1,3,3-tetramethylguanidine; and / or the organic solvent is selected from dichloromethane, toluene, tetramethylolpropane, methylbenzene, methyl benzoate ... One or more of hydrofuran, nitromethane, toluene, chloroform, acetone, N,N-dimethylformamide, dimethyl sulfoxide, acetonitrile, and ethyl acetate; and / or the reaction temperature is -78 to 50° C.; and / or the reaction time is 8 to 24 hours; and / or the amount ratio of the saccharide compound, the base, the imidazolyl sulfide reagent, and the organic solvent is 1 mol: (1.5-7) mol: (1.5-3) mol: (5-10) volume.

7. Use of a glucosinolate compound in constructing a glucosinolate-labeled protein, characterized in that: The glucosinolate compound represented by formula (8) is used as a reaction raw material, and under the action of an oxidant, in an organic solvent, a reaction is performed to obtain an oxidized glucosinolate compound represented by formula (9); then, under the action of a photosensitizer, in a solvent, a reaction is performed to obtain a glucosinolate-labeled protein represented by formula (10). The reaction process is shown in reaction formula (c): in, R is selected from benzyl, acyl, alkyl, and silicon; R 1 is selected from alkenyl and substituted alkenyl; wherein the substituted alkenyl is selected from alkyl substituted alkenyl; and n is selected from an integer of 4-6.

8. The use according to claim 7, characterized in that The ratio of the glucosinolate compound represented by formula (8), the oxidant, and the organic solvent is 1 mol: (2-3) mol: (5-10) volume; the ratio of the oxidized glucosinolate compound represented by formula (9), ribonuclease A, the photosensitizer, and the solvent is (10-100) mol: 1 mol: (1-10) mol: (10-1000) volume; and / or, the oxidant is selected from one or more of hydrogen peroxide and m-chloroperbenzoic acid; the organic solvent is selected from one or more of chloroform, dichloromethane, methanol, and ethanol; And / or, the photosensitizer is selected from one or more of flavin, rose bengal, rhodamine, and iridium trichloride; and / or, the solvent is selected from one or more of DMF, PBS, water, and DMSO; and / or, the reaction temperature for the reaction of the glucosinolate compound to form the oxidized glucosinolate compound is 25-70°C; and / or, the reaction time is 8-16 hours; and / or, the reaction temperature for the reaction of the oxidized glucosinolate compound with the ribonuclease A to form the glucosinolate-labeled protein is 0-50°C; and / or, the reaction time is 1-16 hours.

9. A glucosinolate compound, characterized in that Its structural formula is shown in formula (8): Wherein, R is selected from benzyl, acyl, alkyl, and silicon; R 1 is selected from alkenyl and substituted alkenyl; wherein the substituted alkenyl is selected from alkyl substituted alkenyl; and n is selected from an integer of 4-6.

10. A glucosinolate-labeled protein, characterized in that its structural formula is as shown in formula (10): in, R is selected from benzyl, acyl, alkyl, and silicon; and n is selected from an integer of 4-6.

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