A method for one-pot synthesis of thiosugars by DDQ-mediated glycosyl thiol and xanthene derivative

Abstract

The application discloses a novel method for synthesizing thioglycoside, which is a one-pot method for synthesizing thioglycoside compounds via DDQ-mediated xanthene compounds and glycosyl mercaptan. The method is simple in operation, mild in reaction condition, free of metal catalysis, and good in substrate universality, and is favorable for large-scale production.

Description

Technical Field

[0001] This invention relates to a method for synthesizing thioglycosides, and more particularly to a method for synthesizing thioglycoside compounds by 9-position CS coupling reaction of glycosyl thiols and xanthracene compounds under the action of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), which belongs to the field of bioactive molecule synthesis technology. Background Technology

[0002] In biopharmaceuticals, thioglycosides play an irreplaceable and crucial role. Compared to oxoglycosides, they offer significantly improved hydrolytic stability and bioactivity while maintaining similar conformational preferences. Due to their stable structure and relatively weak CS bond energies, thioglycosides are frequently used as donors in the synthesis of other bioactive drug molecules. Because of their highly efficient bioactivity, thioglycosides are also widely used in biomedicine and other fields. Oxanthracene compounds are also bioactive molecules; molecules carrying this moiety exhibit diverse pharmacological activities, such as in photodynamic therapy, cell imaging, dyes, and fluorescent materials. They are also used as components in the synthesis of bioactive molecules and functional materials. The following structural examples illustrate some instances of thioglycosides as drug molecules, demonstrating their important role as organic synthetic intermediates and in bioactive drugs.

[0003]

[0004] As shown in the structure below, some of the activities exhibited by xanthracene compounds indicate that thioglycosides formed by the linkage of glycosylthiols and xanthracene also exhibit good activity.

[0005]

[0006] Based on previous research on glucosinolates, their role is evident, occupying an indispensable position in chemistry, pharmacy, biomedicine, and materials science. Despite their excellent work, demanding conditions such as high temperatures or the use of metal reagents limit substrate diversity. For example, in recent years, research groups such as Xue, Samir Messioudi, and Maciej A. Walczak have developed methods for synthesizing glucosinolates using metal catalysts such as Pd, Ni, and Cu. This not only advances traditional metal catalysis methods but also develops economical, environmentally friendly, and practical methods utilizing photocatalysis or electrocatalysis. (Chem. Sci. 2018, 9, 8753-8759; Org. Lett. 2019, 21, 5132-5137; J. Am. Chem. Soc. 2018, 140, 18140-18150; Chem. Commun. 2020, 56, 4464-4467; J. Am. Chem. Soc. 2020, 142, 11102-11113). While these methods offer certain advantages and substrate applicability, drawbacks such as high catalyst loading, ligand loading, high temperature, and long reaction time limit the reaction range of the substrates. The following reaction illustrates this:

[0007]

[0008] Numerous reports have documented the modification of xanthenes, systematically and comprehensively elucidating their crucial role. For instance, recent studies have extensively explored the modification of the 9-position of xanthenes using C, N, O, S, P, and various heteroatoms, demonstrating the indispensable position of xanthenes in chemistry (Org. Lett. 2021, 23, 1383-1387; Org. Lett. 2019, 21, 3228-3231; Org. Chem. Front. 2018, 5, 2652-2656; Green Chem. 2019, 21, 798-802).

[0009]

[0010] In this process, R represents alkanes, aromatic hydrocarbons, heterocycles, etc., and X represents heteroatoms such as C, N, O, S, and P. This type of dehydrogenation cross-coupling reaction exhibits advantages such as convenience, simplicity, and atom economy. However, these traditional synthetic methods suffer from drawbacks such as high temperatures, specialized electro-reaction apparatus, and additional catalysts. Furthermore, the traditional 9-position CS coupling reaction is only applicable to aromatic thiols and not to aliphatic thiols (Green Chem., 2019, 21, 798-802). Summary of the Invention

[0011] To address the shortcomings of existing methods for synthesizing thioglycosides, the present invention aims to provide a one-step method for synthesizing thioglycosides using anthracene compounds and glycosylthiols. This method is simple, has mild reaction conditions, requires no metal catalysis, and has good substrate universality, which is beneficial for large-scale production.

[0012] To achieve the above-mentioned technical objectives, the present invention provides a method for synthesizing thioglycosides, which involves performing a 9-position CS coupling reaction between anthracene compounds and glycosylthiols under the action of DDQ to obtain thioglycoside compounds.

[0013] As a preferred embodiment, the glycosylthiol has the structure of Formula 1:

[0014] R1-SH

[0015] Formula 1

[0016] Wherein, R1 is a five-membered sugar ring, a six-membered sugar ring, or a polycyclic sugar ring composed of two or more five-membered or six-membered sugar rings bonded together. Preferred polycyclic sugar rings are two-membered sugar rings. Six-membered sugar rings include glucose rings, and five-membered sugar rings include fructose and ribose, etc. In the glycosyl thiols of the present invention, the hydroxyl groups on the five-membered, six-membered, or polycyclic sugar rings are etherified or acylated; for example, the acylated groups can be acetyl, benzoyl, or pivaloyl, etc.

[0017] As a preferred embodiment, the anthracene compound has the structure of Formula 2:

[0018]

[0019] in,

[0020] R is hydrogen or a C1-C5 alkyl group;

[0021] X is either O or N-R2;

[0022] R2 is a phenyl, phenyl derivative, benzyl, or benzyl derivative.

[0023] R is a substituent group on the benzene ring. R can be hydrogen or a common substituent, such as a short-chain alkyl group, specifically methyl, ethyl, butyl, etc.

[0024] R2 is a substituent on the heteroatom nitrogen. When choosing a phenyl derivative, the phenyl derivative mainly contains common substituents on the benzene ring. These substituents can be electron-withdrawing or electron-donating groups, such as alkyl groups (specifically C1-C5 alkyl groups), alkoxymethyl groups (specifically C1-C5 alkoxy groups), phenyl groups, or halogen substituents (specifically fluorine, chlorine, etc.). When choosing a benzyl derivative, the benzyl derivative mainly contains common substituents on the benzene ring. These substituents can be electron-withdrawing or electron-donating groups, such as alkyl groups (specifically C1-C5 alkyl groups), alkoxymethyl groups (specifically C1-C5 alkoxy groups), phenyl groups, or halogen substituents (specifically fluorine, chlorine, etc.).

[0025] As a preferred embodiment, the thioglycoside compound has the structure of Formula 3:

[0026]

[0027] in,

[0028] R1 is a five-membered sugar ring, a six-membered sugar ring, or a polycyclic sugar ring composed of two or more five-membered or six-membered sugar rings bonded together;

[0029] R is hydrogen or a C1-C5 alkyl group;

[0030] X is either O or N-R2;

[0031] R2 is a phenyl, phenyl derivative, benzyl, or benzyl derivative.

[0032] The thioglycoside compounds of the present invention have good substrate universality, and high yields can be obtained by using different substrates under preferred reaction conditions. The specific structures and yields of the thioglycoside compounds are as follows:

[0033]

[0034]

[0035] As a preferred embodiment, the molar ratio of the glycosylthiol to the anthracene compound is 1:1.2 to 1.5.

[0036] As a preferred embodiment, the molar ratio of the glycosylthiol to DDQ is 1:1.2 to 1.5.

[0037] As a preferred embodiment, the coupling reaction uses dichloromethane as the reaction medium. Experiments show that dichloromethane is a benign solvent for this reaction. Most conventional reaction solvents, such as ethanol, tetrahydrofuran, and acetonitrile, cannot facilitate the reaction, while dichloromethane allows the reaction to proceed smoothly and achieve a high yield, which is unexpected.

[0038] As a preferred embodiment, the coupling reaction conditions are: a reaction temperature of room temperature and a reaction time of 6–8 hours.

[0039] The reaction mechanism for preparing thioglycosides from glycosyl thiols, xanthracene compounds, and DDQ in this invention (using the reaction of oxanthracene and glycosyl thiols as an example) is as follows: oxanthracene 2a undergoes a single-electron transfer under the action of DDQ to form a radical ion pair I. Subsequently, DDQ captures a proton from oxanthracene to form an oxanthracene radical III. Then, a second single-electron transfer process occurs to generate the oxanthracene cation III and DDQH. - Anion. Finally, the glycosylthiosulfate thioanion 1a attacks the xanthracene cation III in a coupling reaction to generate thioglycoside compound 3a.

[0040]

[0041] The method for synthesizing glucosinolates according to the invention includes the following specific steps:

[0042] 1) Add oxane and DDQ to the reaction tube without replacing the nitrogen gas.

[0043] 2) Then dichloromethane is added sequentially as a solvent, and finally glycosyl thiols are added for reaction.

[0044] 2) The system reacts at room temperature and in air for 6 to 8 hours.

[0045] 5) After the reaction is complete, extract with DCM and water, dry, and concentrate under reduced pressure to obtain the target product.

[0046] 6) The petroleum ether / ethyl acetate mixed solvent system is used as the eluent, and the target product can be obtained by column chromatography separation.

[0047] Compared with the prior art, the beneficial technical effects of the technical solution of the present invention are as follows:

[0048] 1) The reaction steps are simple and can be completed in one pot.

[0049] 2) The reaction conditions are mild, no heating is required, and the reaction can be carried out in air.

[0050] 3) No metal catalysts are required, resulting in low cost and easy separation and purification of the target product.

[0051] 4) The raw materials for the reaction are cheap and readily available, and can all be obtained through commercial channels.

[0052] 5) The reaction has good universality, good tolerance to different substrate functional groups, and the target yield is moderate to good.

[0053] 6) The thioglycosides obtained from the reaction contain two active molecules: a sugar moiety and anthracene. Attached Figure Description

[0054] Figure 1 For compound 1 1 H NMR;

[0055] Figure 2 For compound 1 13 C NMR;

[0056] Figure 3 For compound 2 1 H NMR;

[0057] Figure 4 For compound 2 13 C NMR; Detailed Implementation

[0058] The following specific embodiments are intended to further illustrate the content of the present invention, rather than to limit the scope of protection of the claims.

[0059] Unless otherwise specified, the reaction raw materials in the following specific examples are all conventional commercial reagents.

[0060] Optimize the experimental section:

[0061] The following reactions of xanthracene, glycosylthiols, and DDQ under optimal reaction conditions were used as standard reactions to investigate the effect of different reaction conditions on the reactions:

[0062]

[0063] Add xanthracene and oxidant to a clean, dry Schlenk tube, followed by glycosyl thiol and solvent (2 mL). React at room temperature for 8 hours. TLC showed complete reaction of the starting material. Add 2.0 mL of dichloromethane and 2.0 mL of water to the system. Allow to separate naturally into layers. Extract the aqueous phase with dichloromethane (2.0 mL × 3). Combine the organic phases, dry with anhydrous sodium sulfate, filter, and evaporate the solvent to obtain the crude product. Separate by silica gel column chromatography (eluent: ethyl acetate: petroleum ether = 4:1) to obtain the thioglycoside compound.

[0064] product:

[0065] Examples 1-15 below are comparative descriptions based on the above standard reaction, with the oxidant and solvent replaced, etc.

[0066]

[0067]

[0068] Standard reaction conditions: glycosyl thiol (0.1 mmol, 1.0 equiv), xanthracene (0.12 mmol, 1.2 equiv), oxidant (0.12 mmol, 1.2 equiv), solvent (2.0 ml).

[0069] The comparison in the table above shows that common oxidants, such as K2S2O8, BPO, PhI(OAc)2, and PDC, cannot make the reaction proceed smoothly, and DDQ is irreplaceable.

[0070] The comparison in the table above shows that common reaction solvents such as ethanol, THF, and CH3CN cannot make the reaction proceed smoothly, while DCM is the best solvent for the reaction. Specific implementation examples:

[0072] The following specific examples are intended to examine the reaction effects of different substrates under optimal reaction conditions.

[0073]

[0074] Example 1

[0075] Oxanthracene (22 mg, 0.12 mmol, 1.2 equiv) and DDQ (27 mg, 0.12 mmol, 1.2 equiv) were added to a clean, dry Schlenk tube, followed by glycosylthiol 1a (36 mg, 0.1 mmol, 1.0 equiv) and dichloromethane (2 mL). The reaction was carried out at room temperature for 8 hours. TLC showed that the starting material had reacted completely. 2.0 mL of dichloromethane and 2.0 mL of water were added to the system, and the layers separated naturally. The aqueous phase was extracted with dichloromethane (2.0 mL × 3), and the organic phases were combined. The mixture was dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated to obtain the crude product. The crude product was separated by silica gel column chromatography (eluting agent: ethyl acetate: petroleum ether = 4:1) to give thioglycoside compound 1 (93%).

[0076] product:

[0077]

[0078] 1H NMR (400MHz, CDCl3) δ7.38 (ddd, J=11.7, 7.5, 1.5Hz, 2H), 7.30 (ddt, J=9.6, 7. 5,2.6Hz,2H),7.19-7.08(m,4H),5.54(s,1H),5.08-4.96(m,2H),4.92(t,J=9. 4Hz,1H),4.18(d,J=2.5Hz,1H),4.15(d,J=4.4Hz,1H),3.84(dd,J=12.4,2.3H z,1H),3.45-3.30(m,1H),2.06(s,3H),1.98(s,3H),1.94(s,3H),1.84(s,3H). 13 C NMR (100MHz, CDCl3) δ170.8,170.4,169.5,169.4,152.6,152.1,129.6,129.4,129.3,129.1,123.9, 123.6,121.3,120.4,116.8,116.8,82.3,75.7,73.9,69.5,68.1,62.0,42.2,20.9,20.7,20.7,20.7.

[0079] Example 2

[0080] N-Phenylacetidine (32 mg, 0.12 mmol, 1.2 equiv) and DDQ (27 mg, 0.12 mmol, 1.2 equiv) were added to a clean, dry Schlenk tube and dissolved in dichloromethane (2 mL). After stirring at room temperature for 20 minutes, glycosylthiol 1a (36 mg, 0.1 mmol, 1.0 equiv) was added, and the reaction continued for 8 hours. TLC showed that the starting material had reacted completely. 2.0 mL of dichloromethane and 2.0 mL of water were added to the system, and the mixture was allowed to separate naturally. The aqueous phase was extracted with dichloromethane (2.0 mL × 3), and the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated to obtain the crude product. The crude product was separated by silica gel column chromatography (eluting agent: ethyl acetate: petroleum ether = 4:1) to give thioglycoside compound 2 (82%).

[0081] product:

[0082]

[0083] 1H NMR (400MHz, CDCl3) δ7.63(t,J=7.6Hz,2H),7.53(t,J=7.5Hz,1H),7.41-7.31(m,3H),7.31-7.24(m,1H),7.11 (ddd,J=8.6,7.3,1.6Hz,1H),7.05(td,J=8.4,7.8,1.6Hz,1H),6.94(td,J=7.4,6.8,4.1Hz,2H),6.45(d,J=8. 3Hz,1H),6.37(d,J=8.3Hz,1H),5.85(s,1H),5.10-4.98(m,2H),5.00-4.90(m,1H),4.25(dd,J=12.3,5.5Hz,1 H),4.15-4.06(m,2H),3.50(ddd,J=8.1,5.7,2.3Hz,1H),2.15(s,3H),2.02(s,3H),1.96(s,3H),1.87(s,3H). 13 C NMR (100MHz, CDCl3) δ170.8,170.4,169.5,169.3,142.3,142.0,140.3,131.0,130.9,128.9,128.7,128.6,128. 4,128.4,121.4,120.5,119.7,119.1,115.0,114.7,82.0,75.8,74.1,69.8,68.5,62.6,46.6,21.0,20.7,20.7.

[0084] Example 3

[0085] N-(p-methylphenyl)acridine (33 mg, 0.12 mmol, 1.2 equiv) and DDQ (27 mg, 0.12 mmol, 1.2 equiv) were added to a clean, dry Schlenk tube and dissolved in dichloromethane (2 mL). After stirring at room temperature for 20 minutes, glycosylthiol 1a (36 mg, 0.1 mmol, 1.0 equiv) was added, and the reaction continued for 8 hours. TLC showed that the starting material had reacted completely. 2.0 mL of dichloromethane and 2.0 mL of water were added to the system, and the mixture was allowed to separate naturally. The aqueous phase was extracted with dichloromethane (2.0 mL × 3), and the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated to obtain the crude product. Separation by silica gel column chromatography (eluting agent: ethyl acetate: petroleum ether = 4:1) yielded thioglycoside compound 3 (79%).

[0086] product:

[0087]

[0088] 1 H NMR (400MHz, CDCl3) δ7.42(d,J=7.9Hz,2H),7.36(dd,J=7.5,1.6Hz,1H),7.26(dd,J=7.6,1.6Hz,1H),7.21(d,J=8.2Hz,2 H),7.11(ddd,J=8.5,7.3,1.6Hz,1H),7.04(ddd,J=8.5,7.3,1.6Hz,1H),6.93(tdd,J=7.2,5.9,1.1Hz,2H),6.47(dd,J=8. 3,1.0Hz,1H),6.39(dd,J=8.3,1.1Hz,1H),5.85(s,1H),5.10-4.98(m,2H),4.99-4.90(m,1H),4.25(dd,J=12.3,5.5Hz,1H ),4.15-4.05(m,2H),3.49(ddd,J=9.8,5.6,2.1Hz,1H),2.49(s,3H),2.14(s,3H),2.01(s,3H),1.96(s,3H),1.86(s,3H). 13 C NMR (100MHz, CDCl3) δ170.8,170.4,169.5,169.3,142.4,142.2,138.6,137.6,131.5,130.6,128.8,128.5,128.4, 128.3,121.2,120.3,119.7,119.0,115.0,114.7,82.0,75.8,74.1,69.8,68.5,62.5,46.7,21.4,20.9,20.7,20.7.

[0089] Example 4

[0090] N-Biphenyl acridine (40 mg, 0.12 mmol, 1.2 equiv) and DDQ (27 mg, 0.12 mmol, 1.2 equiv) were added to a clean, dry Schlenk tube and dissolved in dichloromethane (2 mL). After stirring at room temperature for 20 minutes, glycosyl thiol 1a (36 mg, 0.1 mmol, 1.0 equiv) was added, and the reaction continued for 8 hours. TLC showed that the starting material had reacted completely. 2.0 mL of dichloromethane and 2.0 mL of water were added to the system, and the mixture was allowed to separate naturally. The aqueous phase was extracted with dichloromethane (2.0 mL × 3), and the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated to obtain the crude product. Separation was performed by silica gel column chromatography (eluting agent: ethyl acetate: petroleum ether = 4:1) to obtain thioglycoside compound 4 (90%).

[0091] product:

[0092]

[0093] 1 1H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 8.4 Hz, 2H), 7.70 (dd, J = 8.3, 1.3 Hz, 2H), 7.56 - 7.48 (m, 2H), 7.46 - 7.36 (m, 4H), 7.29 (dd, J = 7.5, 1.6 Hz, 1H), 7.15 (ddd, J = 8.6, 7.3, 1.6 Hz, 1H), 7.08 (ddd, J = 8.4, 7.3, 1.6 Hz, 1H), 6.99 - 6.94 (m, 2H), 6.56 (dd, J = 8.4, 1.1 Hz, 1H), 6.47 (dd, J = 8.4, 1.1 Hz, 1H), 5.87 (s, 1H), 5.11 - 5.02 (m, 2H), 4.97 (t, J = 9.7 Hz, 1H), 4.27 (dd, J = 12.3, 5.5 Hz, 1H), 4.17 - 4.07 (m, 2H), 3.52 (ddd, J = 8.7, 5.6, 2.2 Hz, 1H), 2.16 (s, 3H), 2.02 (s, 3H), 1.97 (s, 3H), 1.89 (s, 3H). 13 13C NMR (100 MHz, CDCl3) δ 170.8, 170.4, 169.5, 169.3, 142.3, 142.0, 141.6, 140.2, 139.4, 131.3, 129.5, 129.1, 128.9, 128.6, 128.5, 128.4, 127.9, 127.3, 121.4, 120.5, 119.8, 119.1, 115.0, 114.8, 82.0, 75.8, 74.1, 69.8, 68.5, 62.6, 46.6, 21.0, 20.7.

[0094] Example 5

[0095] N-Benzylacridine (33 mg, 0.12 mmol, 1.2 equiv) and DDQ (27 mg, 0.12 mmol, 1.2 equiv) were added to a clean, dry Schlenk tube and dissolved in dichloromethane (2 mL). After stirring at room temperature for 20 minutes, glycosylthiol 1a (36 mg, 0.1 mmol, 1.0 equiv) was added, and the reaction continued for 8 hours. TLC showed that the starting material had reacted completely. 2.0 mL of dichloromethane and 2.0 mL of water were added to the system, and the mixture was allowed to separate naturally. The aqueous phase was extracted with dichloromethane (2.0 mL × 3), and the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated to obtain the crude product. The crude product was separated by silica gel column chromatography (eluting agent: ethyl acetate: petroleum ether = 4:1) to give thioglycoside compound 5 (80%).

[0096] product:

[0097]

[0098] 1 H NMR (400MHz, CDCl3) δ7.37 (dd, J=7.6, 1.6Hz, 1H), 7.35-7.21 (m, 4H), 7.24-7.09 (m, 4H), 6.96 (tdd ,J=7.4,2.9,1.0Hz,2H),6.85(d,J=8.2Hz,1H),6.80(d,J=8.2Hz,1H),5.79(s,1H),5.25(s,2H),5 .11-5.00(m,2H),4.93(t,J=9.5Hz,1H),4.26(dd,J=12.3,5.6Hz,1H),4.17-4.13(m,1H),4.13-4. 10(m,1H),3.54(ddd,J=9.7,5.5,2.3Hz,1H),2.15(s,3H),2.02(s,3H),1.96(s,3H),1.88(s,3H). 13 C NMR (100MHz, CDCl3) δ170.8,170.4,169.5,169.3,141.7,141.4,136.5,129.0,128.8,128.3,127.2,126.3,12 1.3,121.2,120.8,120.5,114.3,113.9,81.9,75.7,74.0,69.8,68.5,62.6,50.6,46.6,21.0,20.8,20.7,20.7

[0099] Example 6

[0100] N-(p-methylbenzyl)acridine (34 mg, 0.12 mmol, 1.2 equiv) and DDQ (27 mg, 0.12 mmol, 1.2 equiv) were added to a clean, dry Schlenk tube and dissolved in dichloromethane (2 mL). After stirring at room temperature for 20 minutes, glycosylthiol 1a (36 mg, 0.1 mmol, 1.0 equiv) was added, and the reaction continued for 8 hours. TLC showed that the starting material had reacted completely. 2.0 mL of dichloromethane and 2.0 mL of water were added to the system, and the mixture was allowed to separate naturally. The aqueous phase was extracted with dichloromethane (2.0 mL × 3), and the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated to obtain the crude product. The crude product was separated by silica gel column chromatography (eluting agent: ethyl acetate: petroleum ether = 4:1) to give thioglycoside compound 6 (78%).

[0101] product:

[0102]

[0103] 1 H NMR (400MHz, CDCl3) δ7.36 (dd, J=7.6, 1.5Hz, 1H), 7.24 (dd, J=7.7, 1.9Hz, 1H), 7.19 (td, J=7.8, 1.6Hz, 1H), 7 .18-7.08(m,3H),7.06(d,J=7.9Hz,2H),6.96(td,J=7.4,3.6Hz,2H),6.85(d,J=8.2Hz,1H),6.80(d,J=8.3Hz, 1H),5.79(s,1H),5.21(s,2H),5.11-4.99(m,2H),4.97-4.90(m,1H),4.26(dd,J=12.3,5.6Hz,1H),4.18-4.0 7(m,2H),3.54(ddd,J=8.7,5.6,2.3Hz,1H),2.33(s,3H),2.15(s,3H),2.02(s,3H),1.96(s,3H),1.88(s,3H). 13 C NMR (100MHz, CDCl3) δ170.8,170.4,169.5,169.3,141.7,141.4,136.8,133.3,129.6,128.8,128.3,126.2,121.3 ,121.1,120.7,120.4,114.3,113.9,81.9,75.7,74.1,69.8,68.6,62.6,50.4,46.7,21.2,21.0,20.8,20.7,20.7.

[0104] Example 7

[0105] N-(4-chlorobenzyl)acridine (37 mg, 0.12 mmol, 1.2 equiv) and DDQ (27 mg, 0.12 mmol, 1.2 equiv) were added to a clean, dry Schlenk tube and dissolved in dichloromethane (2 mL). After stirring at room temperature for 20 minutes, glycosylthiol 1a (36 mg, 0.1 mmol, 1.0 equiv) was added, and the reaction continued for 8 hours. TLC showed that the starting material had reacted completely. 2.0 mL of dichloromethane and 2.0 mL of water were added to the system, and the mixture was allowed to separate naturally. The aqueous phase was extracted with dichloromethane (2.0 mL × 3), and the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated to obtain the crude product. The crude product was separated by silica gel column chromatography (eluting agent: ethyl acetate: petroleum ether = 4:1) to give thioglycoside compound 7 (95%).

[0106] product:

[0107]

[0108] Example 8

[0109] Oxanthracene (22 mg, 0.12 mmol, 1.2 equiv) and DDQ (27 mg, 0.12 mmol, 1.2 equiv) were added to a clean, dry Schlenk tube, followed by glycosylthiol 3a (36 mg, 0.1 mmol, 1.0 equiv) and dichloromethane (2 mL). The reaction was carried out at room temperature for 8 hours. TLC showed that the starting material had reacted completely. 2.0 mL of dichloromethane and 2.0 mL of water were added to the system, and the layers separated naturally. The aqueous phase was extracted with dichloromethane (2.0 mL × 3), and the organic phases were combined. The mixture was dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated to obtain the crude product. The crude product was separated by silica gel column chromatography (eluting agent: ethyl acetate: petroleum ether = 4:1) to give thioglycoside compound 8 (83%).

[0110] product:

[0111]

[0112] 1H NMR(400MHz, CDCl3)δ7.40(dd,J=7.7,1.5Hz,1H),7.34-7.28(m,3H),7.21-7.07(m,4 H),5.53(s,1H),5.25(d,J=3.7Hz,1H),5.21(t,J=10.0Hz,1H),4.89(dd,J=10.0,3.6 Hz,1H),4.33(s,1H),4.27(dd,J=12.3,5.7Hz,1H),3.98(dd,J=12.3,2.4Hz,1H),3.4 9(ddd,J=10.0,5.7,2.5Hz,1H),2.11(s,3H),2.11(s,3H),2.01(s,3H),1.91(s,3H). 13 C NMR (100MHz, CDCl3) δ170.8,170.1,170.1,169.6,153.0,152.5,129.5,129.3,128.9,124.1,123 .5,121.2,120.3,117.3,116.9,80.8,76.6,71.9,70.3,65.8,62.8,42.0,21.0,20.8,20.7,20.6.

[0113] Example 9

[0114] Oxanthracene (22 mg, 0.12 mmol, 1.2 equiv) and DDQ (27 mg, 0.12 mmol, 1.2 equiv) were added to a clean, dry Schlenk tube, followed by glycosylthiol 4a (53 mg, 0.1 mmol, 1.0 equiv) and dichloromethane (2 mL). The reaction was carried out at room temperature for 8 hours. TLC showed that the starting material had reacted completely. 2.0 mL of dichloromethane and 2.0 mL of water were added to the system, and the layers separated naturally. The aqueous phase was extracted with dichloromethane (2.0 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated to obtain the crude product. Separation was carried out by silica gel column chromatography (eluting agent: ethyl acetate: petroleum ether = 20:1) to give thioglycoside 9 (78%).

[0115] product:

[0116]

[0117] 1H NMR (400MHz, CDCl3) δ7.37(dd,J=7.7,1.6Hz,1H),7.29(dd,J=8.6,7.0Hz,3H),7.16-7.06(m,4H),5.47(s,1H),5.18-5.02(m,2H),4.94(dd,J=10 .2,8.8Hz,1H),4.21(d,J=10.2Hz,1H),4.03-3.97(m,2H),3.48(ddd,J=9 .7,4.0,2.5Hz,1H),1.21(s,9H),1.11(s,9H),1.05(s,9H),0.97(s,9H). 13 C NMR (100MHz, CDCl3) δ178.2,177.3,176.5,176.4,152.9,152.3,129.6,129.3,129.2,129.1,123.9,123.4,121. 9,120.5,116.8,116.8,82.6,76.0,73.4,69.3,67.6,62.1,41.9,39.0,38.8,38.8,38.6,27.3,27.2,27.2,27.0.

[0118] Example 10

[0119] Oxanthracene (22 mg, 0.12 mmol, 1.2 equiv) and DDQ (27 mg, 0.12 mmol, 1.2 equiv) were added to a clean, dry Schlenk tube, followed by glycosylthiol 5a (29 mg, 0.1 mmol, 1.0 equiv) and dichloromethane (2 mL). The reaction was carried out at room temperature for 8 hours. TLC showed that the starting material had reacted completely. 2.0 mL of dichloromethane and 2.0 mL of water were added to the system, and the mixture was allowed to separate naturally. The aqueous phase was extracted with dichloromethane (2.0 mL × 3), and the organic phases were combined. The mixture was dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated to obtain the crude product. The crude product was separated by silica gel column chromatography (eluting agent: ethyl acetate: petroleum ether = 5:1) to give thioglycoside compound 10 (88%).

[0120] product:

[0121]

[0122] 1H NMR (400MHz, CDCl3) δ7.39(dd,J=7.8,1.6Hz,1H),7.34-7.25(m,3H),7.16-7.08(m,4H),5.48(s,1H),4.99(t,J=8.0Hz,1H),4.82(td,J=8 .3,5.7Hz,2H),4.32(d,J=8.3Hz,1H),4.05(dd,J=11.8,4.9Hz,1H),3.13(dd,J=11.8,8.6Hz,1H),2.01(s,3H),1.99(s,3H),1.88(s,3H). 13 C NMR (100MHz, CDCl3) δ170.0,169.8,169.4,152.8,152.1,129.6,129.2,129.1,129.0,123. 8,123.5,121.6,120.3,116.8,116.8,82.4,71.8,69.5,68.5,64.7,42.2,20.8,20.8,20.7.

[0123] Example 11

[0124] Oxanthracene (11 mg, 0.06 mmol, 1.2 equiv) and DDQ (14 mg, 0.06 mmol, 1.2 equiv) were added to a clean, dry Schlenk tube, followed by glycosylthiol 6a (17 mg, 0.1 mmol, 1.0 equiv) and dichloromethane (1 mL). The reaction was carried out at room temperature for 8 hours. TLC showed that the starting material had reacted completely. 2.0 mL of dichloromethane and 2.0 mL of water were added to the system, and the layers separated naturally. The aqueous phase was extracted with dichloromethane (2.0 mL × 3), and the organic phases were combined. The mixture was dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated to obtain the crude product. The crude product was separated by silica gel column chromatography (eluting agent: ethyl acetate: petroleum ether = 8:1) to give thioglycoside compound 11 (81%).

[0125] product:

[0126]

[0127] 1H NMR (400MHz, CDCl3) δ7.94(d,J=1.4Hz,1H),7.92(d,J=1.5Hz,1H),7.65-7.58(m,1H),7.48-7.40(m,3H ),7.34(dd,J=7.6,1.6Hz,1H),7.19(ddd,J=8.7,7.4,1.7Hz,1H),7.14-7.02(m,3H),6.99-6.89(m,2H), 5.43(s,1H),5.12(d,J=4.6Hz,1H),4.75(dd,J=6.4,4.6Hz,1H),4.68(dd,J=6.4,2.1Hz,1H),4.45(td,J =4.0,2.1Hz,1H),4.38(dd,J=11.9,4.4Hz,1H),4.32(dd,J=11.9,3.6Hz,1H),1.50(s,3H),1.27(s,3H). 13 C NMR (100MHz, CDCl3) δ166.2,152.7,152.3,133.4,129.8,129.6,129.6,129.2,128.8,128.7,128.7,1 23.7,123.2,122.0,121.5,116.9,116.7,114.5,86.3,82.5,81.9,81.2,65.3,41.8,29.8,26.2,25.0.

[0128] Example 12

[0129] Oxanthracene (33 mg, 0.18 mmol, 1.2 equiv) and DDQ (41 mg, 0.18 mmol, 1.2 equiv) were added to a clean, dry Schlenk tube, followed by glycosylthiol 7a (46 mg, 0.1 mmol, 1.0 equiv) and dichloromethane (3 mL). The reaction was carried out at room temperature for 8 hours. TLC showed that the starting material had reacted completely. 2.0 mL of dichloromethane and 2.0 mL of water were added to the system, and the layers separated naturally. The aqueous phase was extracted with dichloromethane (2.0 mL × 3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated to obtain the crude product. Separation was carried out by silica gel column chromatography (eluting agent: ethyl acetate: petroleum ether = 6:1) to obtain thioglycoside compound 12 (75%).

[0130] product:

[0131]

[0132] 1H NMR (400MHz, CDCl3) δ7.43 (ddd, J=7.8, 3.9, 1.5Hz, 2H), 7.32-7.20 (m, 2H), 7.16-7.03 (m, 4H), 5.45 (s, 1H), 5.15 (dd, J=3.4, 1.4Hz, 1H), 5.07 (dd, J=10.1,3.4Hz,1H),4.95(t,J=9.9Hz,1H),4.91(d,J=1.4Hz,1H),3.91-3 .84(m,1H),2.05(s,3H),2.01(s,3H),1.92(s,3H),0.81(d,J=6.2Hz,3H). 13 C NMR (100MHz, CDCl3) δ170.0,170.0,169.9,152.9,152.0,129.7,129.4,129.3,128.8,123.9,1 23.5,121.7,119.1,117.0,116.9,80.8,71.4,71.0,70.0,67.2,42.3,21.0,20.9,20.7,16.9.

[0133] Example 13

[0134] Oxanthracene (11 mg, 0.06 mmol, 1.2 equiv) and DDQ (14 mg, 0.06 mmol, 1.2 equiv) were added to a clean, dry Schlenk tube, followed by glycosylthiol 8a (28 mg, 0.05 mmol, 1.0 equiv) and dichloromethane (1 mL). The reaction was carried out at room temperature for 8 hours. TLC showed that the starting material had reacted completely. 2.0 mL of dichloromethane and 2.0 mL of water were added to the system, and the layers separated naturally. The aqueous phase was extracted with dichloromethane (2.0 mL × 3), and the organic phases were combined. The mixture was dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated to obtain the crude product. Separation was carried out by silica gel column chromatography (eluting agent: ethyl acetate: petroleum ether = 20:1) to give thioglycoside compound 13 (78%).

[0135] product:

[0136]

[0137] 1H NMR (400MHz, CDCl3) δ7.51 (dd, J=7.9, 1.6Hz, 1H), 7.37 (dd, J=7.7, 1.5Hz, 1H), 7.36-7.20 (m, 17H), 7.19-7.06 (m, 7H), 7.03-6.96(m,2H),5.42(s,1H),5.22(d,J=5.3Hz,1H),4.87(d,J=10.8Hz,1H),4.77(d,J=10.6Hz,1H),4.69(d,J=10.8 Hz, 1H), 4.48 (d, J = 12.3Hz, 1H), 4.42 (d, J = 10.7Hz, 1H), 4.37 (d, J = 12.3Hz, 1H), 4.30 (d, J = 11.8Hz, 1H), 4.20 (d, J = 11. 8Hz,1H),3.83(dt,J=10.0,2.4Hz,1H),3.73-3.56(m,3H),3.48(dd,J=10.7,2.8Hz,1H),2.78(dd,J=10.7,1.9Hz,1H). 13 C NMR (100MHz, CDCl3) δ153.1,151.9,138.7,138.4,138.1,137.6,129.8,129.5,129.0,128.5,128.5,128.3,128.2,128.1,128.1,128.0, 127.8,127.8,127.8,127.7,123.6,123.2,122.6,120.0,116.9,116.7,83.1,82.0,78.6,77.3,75.8,75.3,73.6,71.3,71.1,67.7,40.7.

[0138] Example 14

[0139] Oxanthracene (22 mg, 0.12 mmol, 1.2 equiv) and DDQ (27 mg, 0.12 mmol, 1.2 equiv) were added to a clean, dry Schlenk tube, followed by glycosylthiol 10a (65 mg, 0.1 mmol, 1.0 equiv) and dichloromethane (2 mL). The reaction was carried out at room temperature for 8 hours. TLC showed that the starting material had reacted completely. 2.0 mL of dichloromethane and 2.0 mL of water were added to the system, and the layers separated naturally. The aqueous phase was extracted with dichloromethane (2.0 mL × 3), and the organic phases were combined. The mixture was dried over anhydrous sodium sulfate, filtered, and the solvent was evaporated to obtain the crude product. Separation was carried out by silica gel column chromatography (eluting agent: ethyl acetate: petroleum ether = 2:1) to obtain thioglycoside compound 14 (62%).

[0140] product:

[0141]

[0142] 1 H NMR(400MHz, CDCl3)δ7.38(dd,J=7.7,1.6Hz,1H),7.33-7.27(m,3H),7.16-7.06(m,4H),5.52(s,1H),5.10(t,J=9.3Hz,1H ),5.02(q,J=9.6Hz,2H),4.91-4.81(m,2H),4.44(d,J=7.9Hz,1H),4.34(dd,J=12.5,4.4Hz,1H),4.26(dd,J=12.1,1.9Hz, 1H),4.16(d,J=10.1Hz,1H),3.99(dd,J=11.5,5.0Hz,2H),3.69(t,J=9.6Hz,1H),3.60(ddd,J=9.8,4.4,2.3Hz,1H),3.33( ddd,J=10.0,4.9,1.9Hz,1H),2.10(s,3H),2.05(s,3H),2.05(s,3H),1.99(s,3H),1.97(s,3H),1.95(s,3H),1.84(s,3H). 13 C NMR (100MHz, CDCl3) δ170.6,170.4,169.9,169.7,169.4,169.3,152.7,152.1,129.6,129.4,129.2,129.1,123.9,123.5,121.4, 120.3,117.0,116.9,100.9,82.1,76.6,76.3,73.6,73.1,72.1,71.7,70.0,67.8,62.2,61.6,42.0,21.1,20.8,20.8,20.7,20.6.

[0143] The above description is merely a preferred embodiment of the present invention. The present invention is not limited to the above-described embodiments. Any embodiment that achieves the technical effects of the present invention using the same means should fall within the protection scope of the present invention. Within the protection scope of the present invention, various modifications and variations can be made to the technical solutions and / or implementation methods.

Claims

1. A method for synthesizing glucosinolates, characterized in that: Anthracene compounds and glycosyl thiols undergo a 9-position CS coupling reaction under the action of DDQ to obtain thioglycoside compounds, wherein the coupling reaction uses dichloromethane as the reaction medium. The glycosylthiol has the structure of Formula 1: Formula 1 Wherein, R1 is a five-membered sugar ring, a six-membered sugar ring, or a binary sugar ring composed of two five-membered or six-membered sugar rings bonded together; The anthracene compound has the structure of Formula 2: Formula 2 in, R is hydrogen or a C1~C5 alkyl group; X is either O or N-R2; R2 is a phenyl, benzyl, or derivative thereof substituted with a C1-C5 alkyl, C1-C5 alkoxy, phenyl, or halogen.

2. The method for synthesizing thioglycosides according to claim 1, characterized in that: The thioglycoside compound has the structure of formula 3: Formula 3 in, R1 is a five-membered sugar ring, a six-membered sugar ring, or a binary sugar ring composed of two five-membered or six-membered sugar rings bonded together; R is hydrogen or a C1~C5 alkyl group; X is either O or N-R2; R2 is a phenyl, benzyl, or derivative thereof substituted with a C1-C5 alkyl, C1-C5 alkoxy, phenyl, or halogen.

3. The method for synthesizing thioglycosides according to claim 1, characterized in that: The molar ratio of the glycosylthiol to the anthracene compound is 1:1.2~1.

5.

4. The method for synthesizing glucosinolates according to claim 1, characterized in that: The molar ratio of the glycosylthiol to DDQ is 1:1.2~1.

5.

5. A method for synthesizing thioglycosides according to any one of claims 1 to 4, characterized in that: The conditions for the coupling reaction are: the reaction temperature is room temperature and the reaction time is 6-8 h.

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