A method for constructing S-N bond by electrochemical oxidation of glycosyl thiol and amine compound to synthesize glycosyl sulfenamide

Abstract

The application discloses a method for constructing S-N bond by electrochemical oxidation of glycosyl mercaptan and amine compound to synthesize glycosyl sulfenamide, and belongs to the technical field of drug intermediate synthesis. The method uses an organic solution containing glycosyl mercaptan, amine compound and electrolyte salt as an electrolyte, places an anode and a cathode in the electrolyte, passes direct current, and performs electrochemical reaction to obtain a glycosyl sulfenamide compound. The method has strong reaction universality, high yield of target product, and is realized by one-step chemical reaction, and has mild reaction conditions and does not need any transition metal catalyst.

Description

Technical Field

[0001] This invention relates to a method for constructing an SN bond, and more particularly to a method for synthesizing glycosylsulfenamide by electrochemically oxidizing glycosylthiols and amine compounds to construct an SN bond, belonging to the field of pharmaceutical intermediate synthesis technology. Background Technology

[0002] Sumo glycosides are a class of glycosidic compounds that link sugar groups to aglycones via sulfur atoms. They possess a variety of important biological activities and physiological functions in vivo. These compounds exhibit significant biological activities, including antioxidant, anti-inflammatory, antibacterial, and antiviral effects. Therefore, sumo glycosides have broad application prospects in the health and pharmaceutical fields, and their synthesis and bioactivity research has become a research hotspot in biochemistry and medicinal chemistry. Compared to easily hydrolyzed oxyglycosides, sumo glycosides possess stronger acid-base and enzymatic hydrolysis tolerance. They exhibit excellent glycosidase inhibitory activity. Furthermore, due to the relatively weak bond energy of their CS bond, this characteristic allows them to serve as both donors and acceptors, making them widely used in the synthesis of N-glycosides, C-glycosides, oligosaccharides, and polysaccharides. In addition, sumo glycosides are widely found in pharmaceuticals, natural products, and bioactive substances. For example, auranofin is widely used to treat arthritis and also exhibits anticancer activity. hSGLT1 inhibitors can effectively inhibit the absorption of glucose and galactose in the human body and are commonly used diabetes drugs in clinical practice. Calicacamicin gamma and Hsp 90 exhibit good antitumor activity. Afrostyraxthioside A has shown clinical efficacy against nematode parasites. MUS-CB is a fluorescent non-hydrolyzable analog of cellulase, and so on. Among the various thioglycosides developed to date, glycosylsulfenamides are particularly noteworthy. This class of stable thioglycoside compounds has wide applications in industrial and medicinal chemistry. However, to date, only a few reports have been published on the preparation of S-glycosylsulfenamides. Itzstein and colleagues reported a method for preparing thiosylsulfenamides from glycosyl thiols and secondary amines catalyzed by alkyl halides (Owen, DJ; von Itzstein, M., A one-pot synthesis of novel N,N-dialkyl-S-glycosylsulfenamides. Carbohydrate Research 2000, 328, 287-292.). Szilagyi and colleagues reported a silver-catalyzed reaction of disulfide compounds with amines to synthesize glycosylsulfenamides (Illyés, T.-Z.; Molnár-Gábor, D.; Szilagyi, L., Novel approaches to the synthesses of N-substituted S-glycosyl-sulfenamides. Carbohydrate Research 2004, 339, 1561-1564.).Misra and colleagues reported an NBS-catalyzed reaction of glycosyl thiols with amines to synthesize sulfenamides; however, this method requires a low temperature of -40°C (Gucchait, A.; Jana, K.; Misra, AK, Convenient preparation of thioglycomimetics: S-glycosylsulfenamides, sulfinamides and sulphonamides. RSC Advances 2017, 7, 32478-32487.). Gang He and colleagues reported a copper-catalyzed method for synthesizing sulfenamides from glycosyl thiols with 3-methyldioxazolone (Bai, Z.; Zhu, S.; Hu, Y.; Yang, P.; Chu, X.; He, G.; Wang, H.; Chen, G., Synthesis of N-acyl sulfenamides via copper catalysis and their use as S-sulfenylating reagents of thiols. Nature Communications 2022, 13.). However, these methods still require the use of metal catalysts and oxidants. Therefore, developing a green and environmentally friendly method to synthesize this type of compound is of great significance.

[0003] Summary of the Invention

[0004] To address the technical problems existing in the prior art, the purpose of this invention is to provide a method for the efficient synthesis of glycosyl sulfenamides by electrochemically oxidizing glycosyl thiols and amine compounds to construct SN bonds. This method is completed through a one-step electrochemical reaction, with high yield of the target product, simple experimental operation, mild conditions, and broad substrate applicability. It does not require the addition of any metal catalysts, oxidants, reducing agents, or other environmentally harmful chemical reagents, which is beneficial for the efficient synthesis of glycosyl sulfenamides.

[0005] To achieve the above-mentioned technical objectives, this invention provides a method for synthesizing glycosyl sulfenamides by electrochemically oxidizing glycosyl thiols and amine compounds to construct an SN bond. This method utilizes compounds comprising glycosyl thiols and amines...

[0006] An organic solution of a substance and an electrolyte salt is used as the electrolyte. An anode and a cathode are placed in the electrolyte, and a direct current is passed through to carry out an electrochemical reaction to obtain a glycosyl sulfenamide compound.

[0007] As a preferred embodiment, the glycosylthiol has the structure of Formula 1:

[0008] R-SH

[0009] Formula 1

[0010] Wherein, R represents a five-membered, six-membered, or multi-membered sugar ring. A multi-membered sugar ring is composed of two or more five-membered or six-membered sugar rings bonded together, with a preferred multi-membered sugar ring being a two-membered sugar ring. A six-membered sugar ring is such as glucose.

[0011] As a preferred embodiment, the amine compound has the structure of Formula 2:

[0012]

[0013] Among them, R 1 and R 2 Independently selected from hydrogen, primary carbon, secondary carbon, or quaternary carbon, and R 1 and R 2 They are not both hydrogen.

[0014] As a preferred embodiment, the glycosylsulfenamide compound has the structure of Formula 3:

[0015]

[0016] in,

[0017] R can be a five-membered sugar ring, a six-membered sugar ring, or a polysaccharide ring;

[0018] R 1 and R 2 Independently selected from hydrogen, primary carbon, secondary carbon, or quaternary carbon, and R 1 and R 2 They are not both hydrogen.

[0019] In the amine compounds and glycosyl sulfenamide compounds of the present invention, R 1 and R 2 The carbon can be selected from hydrogen, primary carbon, secondary carbon, or quaternary carbon. Primary, secondary, and quaternary carbons have a wide range of sources, including aliphatic hydrocarbon groups and their derivatives, aromatic groups and their derivatives, etc. Aliphatic hydrocarbon groups include, for example, C1 to C12. 10 Alkyl groups. Aliphatic hydrocarbon derivatives, for example, those at C1 to C2. 10 The alkyl group is further substituted with some conventional small molecule substituents, such as halogen substituents, hydroxyl groups, phenyl groups, etc. Aromatic groups include phenyl, naphthyl, etc. Aromatic derivatives are those in which conventional small molecule substituents are further substituted on the benzene ring, such as short-chain alkyl groups, alkoxy groups, halogen substituents, etc. R 1 and R 2 It can be a closed-ring structure, such as a five- or six-membered ring structure. The closed-ring structure can be doped with heteroatoms, such as oxygen or sulfur. Small molecule substituents, such as phenyl or hydroxyl groups, can be further substituted into the closed-ring structure. Essentially, R... 1 and R2 It is a group introduced by amine compounds. In the existing technology, the primary or secondary amines are commonly adapted to the synthesis of glycosyl sulfenamide compounds.

[0020] The glycosyl sulfenamide compound of the present invention has the following structure:

[0021]

[0022]

[0023] The glycosyl sulfenamide compounds of the present invention mainly utilize sugars to thioglycolate existing drugs (such as reboxetine), thereby introducing thioglycoside fragments onto the amino group.

[0024] As a preferred embodiment, the molar ratio of the glycosylthiol to the amine compound is 1:1.5 to 2.5. More preferably, the molar ratio of the glycosylthiol to the amine compound is 1.0:2.0.

[0025] As a preferred embodiment, the molar ratio of the glycosylthiol to the electrolyte salt is 1.0:0.5 to 1.5.

[0026] As a preferred embodiment, the electrolyte salt comprises sodium iodide and / or potassium iodide. Sodium iodide is the most preferred electrolyte salt. Sodium iodide has a significant promoting effect on the reaction; for example, using other electrolyte salts as substitutes would significantly reduce the yield of the glycosylsulfenamide compound.

[0027] As a preferred embodiment, the electrolyte uses acetonitrile and water as a mixed solvent. More preferably, the electrolyte is acetonitrile / water (in a volume ratio of 80-90% / 10-20%). Using a combination of acetonitrile and water as the solvent improves the solubility of the reactants and the electrolyte, and also improves conductivity, thereby increasing the reaction yield of the glycosyl sulfenamide compound.

[0028] As a preferred embodiment, the anode is a carbon rod anode or a platinum sheet anode; the cathode is a platinum sheet cathode, a carbon rod cathode, or a nickel sheet cathode. Experiments show that the most preferred electrode combination is a carbon rod anode and a platinum sheet cathode, which significantly improves the yield of glycosyl sulfenamide compounds compared to other electrode combinations.

[0029] As a preferred embodiment, the electrochemical reaction conditions are as follows: under air conditions, a direct current of 5–15 mA, a temperature of 20–30 °C, and a reaction time of 40–50 min. More preferably, the direct current is 10–15 mA. Within this selected range, increasing the direct current significantly improves the yield of the glycosyl sulfenamide compound. Furthermore, a direct current of 10–15 mA, along with optimized reaction conditions, ensures a yield of over 85% for the glycosyl sulfenamide compound.

[0030] This invention provides a method for synthesizing glycosyl sulfenamides by electrochemically oxidizing glycosyl thiols and amine compounds to construct SN bonds. Taking the reaction between glycosyl thiols and morpholine as an example, the reaction mechanism is as follows: glycosyl thiols undergo oxidation at the anode, losing one electron to become carbonyl thiols free radicals. At the same time, morpholine also undergoes oxidation at the anode, becoming nitrogen free radicals. Then, the carbonyl thiols free radicals and nitrogen free radicals undergo cross-coupling to form sulfenamide compound 3a. Meanwhile, hydrogen protons undergo reduction at the cathode to become hydrogen gas.

[0031]

[0032] The method for synthesizing thioglycosides of the present invention includes the following specific steps:

[0033] 1) At room temperature, glycosyl thiols (0.2 mmol, 1.0 equiv), amine compounds (0.4 mmol, 2 equiv), NaI (0.2 mmol, 1 equiv), and CH3CN / H2O (2.6 mL / 0.4 mL) were added to an integrated electrolytic cell. A carbon rod electrode was used as the anode of the electrochemical system, and a platinum sheet electrode was used as the cathode of the electrochemical system. A direct current of 15 mA was applied.

[0034] 2) Simultaneously, dissolve glycosyl thiols in 1 mL of CH3CN and add them dropwise into the above electrochemical reaction system over 30 min. After the addition is complete, react for another 10 min. Once the reaction is complete, concentrate under reduced pressure to obtain the crude product. Separate the target product by column chromatography.

[0035] Compared with the prior art, the beneficial technical effects of the technical solution of the present invention are as follows:

[0036] 1) The reaction conditions are mild and do not require heating.

[0037] 2) It avoids the use of environmentally unfriendly chemical reagents such as transition metal catalysts, oxidants, and reducing agents.

[0038] 3) The substrate is highly versatile, with both electron-withdrawing and electron-donating protecting groups being well compatible with the reaction. Furthermore, primary amines, secondary amines, cyclic amines, and chain amines can all be obtained in moderate to high yields. Attached Figure Description

[0039] Figure 1 For compound 1 1 H NMR.

[0040] Figure 2 For compound 1 13 C NMR.

[0041] Figure 3 For compound 2 1 H NMR.

[0042] Figure 4 For compound 2 13 C NMR.

[0043] Figure 5 For compound 3 1 H NMR.

[0044] Figure 6 For compound 3 13 C NMR.

[0045] Figure 7 For compound 4 1 H NMR.

[0046] Figure 8 For compound 4 13 C NMR.

[0047] Figure 9 For compound 5 1 H NMR.

[0048] Figure 10 For compound 5 13 C NMR.

[0049] Figure 11 For glucosinolated reboxetine 1 H NMR.

[0050] Figure 12 For glucosinolated reboxetine 13 C NMR. Detailed Implementation

[0051] 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.

[0052] This invention uses the electrochemical reaction of glycosylthiols and morpholine to synthesize glycosylsulfenamide compounds as an example for specific illustration, with the optimal reaction conditions selected as the standard reaction conditions. The specific reaction formula is as follows:

[0053]

[0054] At room temperature, 1a (0.2 mmol, 1.0 equiv), 3a (0.4 mmol, 2 equiv), NaI (0.2 mmol, 1 equiv), and CH3CN / H2O (2.6 mL / 0.4 mL) were added to an integrated electrolytic cell. A carbon rod electrode was used as the anode of the electrochemical system, and a platinum sheet electrode was used as the cathode. A 15 mA DC current was applied. At the same time, glycosylthiol 1a was dissolved in 1 mL of CH3CN and added dropwise to the above electrochemical reaction system over 30 min. After the addition was complete, the reaction was allowed to proceed for another 10 min. After the reaction was completed, the product was concentrated under reduced pressure to obtain the crude product, which was then separated by column chromatography to obtain the target product.

[0055] The following control groups 1-12 are compared and explained using standard reaction conditions as a reference:

[0056]

[0057] The reaction conditions are as follows: 1a (0.2 mmol, 1.0 equiv), 3a (0.4 mmol, 2.0 equiv), NaI (0.2 mmol, 1.0 equiv), solvent (4 mL), 40 min.

[0058] The experiment groups 1-4 in the table above investigated the effect of different solvents on the dehydrogenation coupling reaction. The experiment showed that the solvent has a certain influence on the reaction. The reaction can proceed smoothly in polar organic solvents such as DMAc and CH3CN, while the reaction effect is relatively poor in non-polar organic solvents such as DCM. The introduction of a small amount of water into the polar organic solvent can improve the reaction effect. The optimal reaction solvent is a mixture of CH3CN and water.

[0059] The experimental groups 1 and 5-6 in the table above investigated the effects of different electrodes on the dehydrogenation coupling reaction. The experiments showed that the electrode pair has a certain influence on the reaction. Any combination of platinum sheet electrode, carbon rod electrode, nickel sheet electrode, etc. can make the reaction proceed smoothly. The optimal electrode pair is carbon rod as anode and platinum sheet electrode as cathode.

[0060] The experimental groups 1 and 7-8 in the table above investigated the effect of different current magnitudes on the dehydrogenation coupling reaction. The experiments showed that the current magnitude has a certain influence on the reaction. As the current increases, the yield of the target product increases significantly. The preferred reaction current is 10-15 mA, and the optimal reaction current is 15 mA.

[0061] The experimental groups 1 and 9-10 in the table above investigated the effects of different electrolytes on the dehydrogenation coupling reaction. The experiments showed that the electrolyte salt has a certain influence on the reaction. The preferred electrolyte salt is iodine salt, and the optimal electrolyte salt is NaI.

[0062] In the table above, experimental groups 1 and 11 investigated the effect of direct current on the dehydrogenation coupling reaction. Without direct current, the reaction could not proceed smoothly.

[0063] The experimental groups 1 and 12 in the table above investigated the effect of nitrogen atmosphere on the dehydrogenation coupling reaction. The experiments showed that nitrogen has a huge impact on the reaction, and the optimal reaction condition is an air atmosphere.

[0064] The following examples examine the reaction effects of different substrates under optimal reaction conditions.

[0065] Example 1

[0066]

[0067] At room temperature, 3a (0.4 mmol, 2 equiv), NaI (0.2 mmol, 1 equiv), and CH3CN / H2O (2.6 mL / 0.4 mL) were added to an integrated electrolytic cell. A carbon rod electrode was used as the anode and a platinum sheet electrode as the cathode. A 15 mA DC current was applied. Simultaneously, 1a was dissolved in 1 mL of CH3CN and added dropwise to the electrochemical reaction system over 30 min. After the addition was complete, the reaction was allowed to proceed for another 10 min. The reaction was then concentrated under reduced pressure to obtain the crude product. The target product 1 (4a, 84.4 mg) was obtained by column chromatography, with a yield of 94%.

[0068]

[0069] (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(morpholinothio)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0070] Yield: 94%;

[0071] The characterization data of this compound are as follows: 1H NMR (400MHz, DMSO-d6) δ5.34(t,J=9.4Hz,1H),5.24(d,J=10.2Hz,1H),4.95-4.82(m,2H),4.19-3.96(m, 3H), 3.56 (t, J = 4.5Hz, 4H), 3.04-2.93 (m, 2H), 2.90-2.84 (m, 2H), 2.00 (s, 3H), 2.00 (s, 6H), 1.94 (s, 3H). 13 C NMR (101MHz, DMSO-d6) δ169.93,169.54,169.31,169.08,82.78,73.97,73.16,68.16,67.49,66.87,62.03,56.67,20.46,20.44,20.38,20.29.

[0072] Example 2

[0073] At room temperature, 3a (0.4 mmol, 2 equiv), NaI (0.2 mmol, 1 equiv), and CH3CN / H2O (2.6 mL / 0.4 mL) were added to an integrated electrolytic cell. A carbon rod electrode served as the anode and a platinum sheet electrode as the cathode. A 15 mA direct current was applied. Simultaneously, 1b was dissolved in 1 mL of CH3CN and added dropwise to the electrochemical reaction system over 30 min. After the addition was complete, the reaction was allowed to proceed for another 10 min. The reaction was then concentrated under reduced pressure to obtain the crude product. Target product 2 (84.4 mg) was obtained by column chromatography, with a yield of 94%.

[0074]

[0075] (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(thiomorpholinothio)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0076] Yield: 94%;

[0077] The characterization data of this compound are as follows: 1H NMR (400MHz, DMSO-d6) δ5.30(d,J=3.4Hz,1H),5.26(d,J=4.3Hz,1H),5.23(d,J=3.9Hz,1H),4.96(t,J=8.0Hz,1H),4.30(t,J= 6.3Hz,1H),4.09-3.95(m,2H),3.56(t,J=4.5Hz,4H),3.04-2.84(m,4H),2.12(s,3H),2.02(s,3H),1.99(s,3H),1.92(s,3H). 13 C NMR (101MHz, DMSO-d6) δ169.98,169.87,169.53,169.36,82.99,73.09,71.18,67.61,66.97,64.92,61.72,56.55,20.59,20.50,20.44,20.40.

[0078] Example 3

[0079] At room temperature, 3a (0.4 mmol, 2 equiv), NaI (0.2 mmol, 1 equiv), and CH3CN / H2O (2.6 mL / 0.4 mL) were added to an integrated electrolytic cell. A carbon rod electrode served as the anode and a platinum sheet electrode as the cathode. A 15 mA DC current was applied. Simultaneously, 1c was dissolved in 1 mL of CH3CN and added dropwise to the electrochemical reaction system over 30 min. After the addition was complete, the reaction was allowed to proceed for another 10 min. The reaction was then concentrated under reduced pressure to obtain the crude product. Target product 3 (45.8 mg) was obtained by column chromatography, with a yield of 61%.

[0080]

[0081] (2R,3R,4S,5S,6R)-2-(acetoxymethyl)-6-(morpholinothio)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0082] Yield: 61%;

[0083] The characterization data of this compound are as follows: 1H NMR(400MHz,DMSO-d6)δ5.85(d,J=1.2Hz,1H),5.21(dd,J=3.4,1.5Hz,1H),5.11(t, J=10.0Hz,1H),4.79(dd,J=10.0,3.5Hz,1H),4.38(ddd,J=10.0,5.8,2.5Hz,1H),4.1 9(dd,J=12.2,5.9Hz,1H),4.06(dd,J=12.3,2.5Hz,1H),3.56(t,J=4.6Hz,4H),3.02 (dtd,J=16.4,11.6,4.4Hz,4H),2.12(s,3H),2.04(s,3H),2.00(s,3H),1.94(s,3H). 13 C NMR (101MHz, DMSO-d6) δ170.02,169.69,169.67,169.54,81.92,69.35,69.32,68.52,66.93,65.69,62.09,56.07,20.68,20.46,20.45,20.37.

[0084] Example 4

[0085] At room temperature, 3b (0.4 mmol, 2 equiv), NaI (0.2 mmol, 1 equiv), and CH3CN / H2O (2.6 mL / 0.4 mL) were added to an integrated electrolytic cell. A carbon rod electrode served as the anode and a platinum sheet electrode as the cathode. A 15 mA direct current was applied. Simultaneously, 1a was dissolved in 1 mL of CH3CN and added dropwise to the electrochemical reaction system over 30 min. After the addition was complete, the reaction was allowed to proceed for another 10 min. The reaction was then concentrated under reduced pressure to obtain the crude product. Target product 4 (85.5 mg) was obtained by column chromatography, with a yield of 92%.

[0086]

[0087] (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(thiomorpholinothio)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0088] Yield: 92%;

[0089] The characterization data of this compound are as follows: 1H NMR(400MHz,CD3OD)δ5.31(t,J=9.3Hz,1H),5.10-5.03(m,1H),4.87(d,J=10 .1Hz,1H),4.25(dd,J=12.3,5.1Hz,1H),4.15(dd,J=12.3,2.3Hz,1H),3.92( ddd,J=10.1,5.0,2.3Hz,1H),3.37-3.32(m,1H),3.29(s,1H),3.27-3.20(m, 2H),2.72-2.58(m,4H),2.06(s,3H),2.02(s,3H),2.02(s,3H),1.98(s,3H). 13 C NMR (101MHz, CD3OD) δ172.26,171.66,171.28,171.12,86.41,76.52,75.61,69.66,69.26,63.39,60.87,29.40,20.73,20.61,20.58.

[0090] Example 5

[0091] At room temperature, 3c (0.4 mmol, 2 equiv), NaI (0.2 mmol, 1 equiv), and CH3CN / H2O (2.6 mL / 0.4 mL) were added to an integrated electrolytic cell. A carbon rod electrode served as the anode and a platinum sheet electrode as the cathode. A 15 mA direct current was applied. Simultaneously, 1a was dissolved in 1 mL of CH3CN and added dropwise to the electrochemical reaction system over 30 min. After the addition was complete, the reaction was allowed to proceed for another 10 min. The reaction was then concentrated under reduced pressure to obtain the crude product. The target product 5 (85.5 mg) was obtained by column chromatography, with a yield of 92%.

[0092]

[0093] (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-((4-hydroxypiperidin-1-yl)thio)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0094] Yield: 92%;

[0095] The characterization data of this compound are as follows: 1H NMR (400MHz, DMSO-d6) δ5.33(t,J=9.4Hz,1H),5.12(d,J=10.2Hz,1H),4.86(t,J =9.8Hz,2H),4.58(d,J=4.2Hz,1H),4.17-4.08(m,1H),4.07-3.99(m,2H),3.44(d q,J=8.5,4.3Hz,1H),3.12-3.02(m,1H),3.00-2.92(m,1H),2.92-2.77(m,2H),2 .00(s,3H),1.99(s,6H),1.94(s,3H),1.69(d,J=11.0Hz,2H),1.51-1.33(m,2H). 13 C NMR (101MHz, DMSO-d6) δ169.92,169.56,169.32,169.04,83.31,73.98,73.29,68. 13,67.57,64.75,61.96,55.33,54.74,35.44,35.28,20.47,20.46,20.40,20.31.

[0096] Example 6

[0097] Thioglycosylation of reboxetine: Reboxetine is a norepinephrine reuptake inhibitor used clinically to treat depression. Both reboxetine and its derivative, reboxetine mesylate, are approved antidepressants. Therefore, the synthesis of reboxetine derivatives is of great significance for the development of such drugs. The inventors successfully introduced a thioglycoside fragment onto the amino group using this electrochemistry to obtain a thioglycosylated reboxetine derivative, yielding the target compound in 42% yield.

[0098]

[0099] (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(((S)-2-((S)-(2-ethoxyphenoxy)(phenyl)methyl)morpholino)thio)tetrahydro-2H-pyran-3,4,5-triyl triacetate

[0100] The characterization data of this compound are as follows: 1H NMR(400MHz,DMSO-d6)δ7.40(d,J=7.5Hz,1H),7.32(t,J=7.3Hz,2H),7.26(d,J=7.1Hz,1H),6.88(dd,J=15.5,7.9Hz,2H),6.80(t,J=7.7Hz,1H),6.71(t,J=7.8Hz,1H),5.32(t,J=9.5Hz,1H),5.27(d,J=6.0Hz,1H),5.14(d,J=10.2Hz,1H),4.85(q,J=11.2,10.6Hz,2H),4.02(q,J=12.4,11.5Hz,5H),3.81(d,J=10.0Hz,2H),3.49(t,J=11.1Hz,1H),3.04-2.77(m,3H),2.45(d,J=11.7Hz,1H),1.99(s,6H),1.93(s,3H),1.82(s,3H),1.41-1.28(m,3H). 13 C NMR(101MHz,DMSO-d6)δ169.94,169.55,169.29,168.77,149.13,147.27,137.58,128.17,127.96,127.36,121.74,120.69,117.02,114.44,83.18,80.89,78.53,74.04,73.15,68.08,67.48,66.58,64.07,62.02,57.24,56.69,20.46,20.38,20.30,20.25。

Claims

1. A method for synthesizing glycosylsulfenamides by electrochemically oxidizing glycosylthiols and amine compounds to form an SN bond, characterized in that: An organic solution containing glycosyl thiols, amine compounds, and electrolyte salts is used as the electrolyte. A carbon rod anode and a platinum cathode are placed in the electrolyte, and a direct current is passed through to carry out an electrochemical reaction to obtain glycosyl sulfenamide compounds. The electrolyte salt includes sodium iodide and / or potassium iodide; The electrolyte uses acetonitrile and water as a mixed solvent; The conditions for the electrochemical reaction are as follows: under air or a protective atmosphere, the magnitude of the direct current is 5-15 mA, the temperature is 20-30 °C, and the time is 40-50 min.

2. The method for synthesizing glycosylsulfenamide by electrochemical oxidation of glycosylthiols and amine compounds to form an SN bond, as described in claim 1, is characterized in that: The glycosylthiol has the structure of Formula 1: Formula 1: ; Wherein, R is a five-membered sugar ring, a six-membered sugar ring, or a polyglycan ring.

3. The method for synthesizing glycosylsulfenamide by electrochemical oxidation of glycosylthiols and amine compounds to form an SN bond, as described in claim 1, is characterized in that: The amine compound has the structure of Formula 2: Formula 2: ; Among them, R 1 and R 2 Independently selected from hydrogen, primary carbon, secondary carbon, or quaternary carbon, and R 1 and R 2 They are not both hydrogen.

4. The method for synthesizing glycosylsulfenamide by electrochemical oxidation of glycosylthiols and amine compounds via SN bonds according to claim 1, characterized in that: The glycosylsulfenamide compound has the structure of Formula 3: Formula 3: ; in, R can be a five-membered sugar ring, a six-membered sugar ring, or a polysaccharide ring; R 1 and R 2 Independently selected from hydrogen, primary carbon, secondary carbon, or quaternary carbon, and R 1 and R 2 They are not both hydrogen.

5. The method for synthesizing glycosylsulfenamide by electrochemical oxidation of glycosylthiols and amine compounds to form an SN bond, according to any one of claims 1 to 4, characterized in that: The molar ratio of the glycosylthiol to the amine compound is 1:1.5~2.

5.

6. The method for synthesizing glycosylsulfenamide by electrochemical oxidation of glycosylthiols and amine compounds to form an SN bond, according to any one of claims 1 to 4, characterized in that: The molar ratio of the glycosyl thiol to the electrolyte salt is 1.0:0.5~1.5.

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