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Preparation method and application of peracetyl-protected 1-thioglucose and glucose 1-mercaptan

A technology of glucosinolate and glucose, which is applied in the fields of medicine and sugar chemical synthesis, can solve the problems of inability to proceed, no effect, low solubility, etc., and achieve high reaction efficiency and yield, no irritation and odor, and mild conditions Effect

Active Publication Date: 2021-03-23
HUAZHONG UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The inventor of the present application conjectures and confirms through experiment, why traditional one-step method uses the thioacetic acid of poisonous malodorous, and does not directly use potassium thioacetate, is because using potassium thioacetate under traditional one-step method condition can cause very low yield
This result may be due to the very small solubility of potassium thioacetate in the solvent dichloromethane at room temperature
So, is it feasible to replace the solvent with dimethylformamide, which has better solubility to potassium thioacetate, under the traditional one-step method? The experimental results show that under these conditions, the reaction cannot proceed at all, even if the reaction temperature is raised, it has no effect

Method used

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  • Preparation method and application of peracetyl-protected 1-thioglucose and glucose 1-mercaptan
  • Preparation method and application of peracetyl-protected 1-thioglucose and glucose 1-mercaptan
  • Preparation method and application of peracetyl-protected 1-thioglucose and glucose 1-mercaptan

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Experimental program
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Effect test

Embodiment 1

[0043] Weigh 1,2,3,4,6-penta-O-acetyl-D-glucose (1g, 2.6mmol) and dissolve it in ethyl acetate (15mL), add potassium thioacetate (590mg, 5.2mmol), Stir and mix, add boron trifluoride diethyl ether (1.3mL, 10.4mmol), react at a constant temperature of 50°C for 4 hours, cool the reaction solution to room temperature, add triethylamine dropwise to neutralize to pH = 7, concentrate under reduced pressure and column Chromatography yielded 987 mg of 2,3,4,6-tetra-O-acetyl-1-S-acetyl-β-D-glucose with a yield of 95%. 1 H NMR (400MHz, CDCl 3 ): δ5.29-5.24(2H,m,H-3,H-1),5.15-5.08(2H,m,H-2,H-4),4.26(1H,dd,J=12.4Hz,J =4.4Hz, H-6a), 4.09(1H, dd, J=12.4Hz, J=2.0Hz, H-6b), 3.83(1H, ddd, J=10.0Hz, J=4.4Hz, J=2.0Hz ,H-5),2.38(3H,s,SCOCH 3 ),2.07,2.03,2.02,2.00(12H,4×s,COCH 3 ).

Embodiment 2

[0045] Under traditional one-step conditions, direct use of potassium thioacetate leads to extremely low yields:

[0046] Weigh 1,2,3,4,6-penta-O-acetyl-D-glucose (1g, 2.6mmol) and dissolve it in dichloromethane (15mL), add potassium thioacetate (590mg, 5.2mmol), Stir and mix, add boron trifluoride diethyl ether (578 μL, 5.2 mmol), react at room temperature for 24 hours, dropwise add triethylamine to neutralize to pH = 7, concentrate under reduced pressure and column chromatography to obtain 2,3,4,6-tetra -O-acetyl-1-S-acetyl-β-D-glucose 312 mg, yield 30%.

Embodiment 3

[0048] Under the traditional one-step process conditions, the use of potassium thioacetate while using dimethylformamide as a solvent causes the raw materials to not react:

[0049] Weigh 1,2,3,4,6-penta-O-acetyl-D-glucose (1g, 2.6mmol) and dissolve it in dimethylformamide (15mL), add potassium thioacetate (590mg, 5.2mmol ), stirring and mixing, adding boron trifluoride diethyl ether (578 μL, 5.2 mmol), and reacting at a constant temperature of 50° C. for 4 hours, the raw materials did not react, and the yield was 0.

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Abstract

The invention belongs to the technical field of medicine and sugar chemical synthesis, and particularly relates to a preparation method and application of peracetyl-protected 1-thioglucose and glucose1-mercaptan. The preparation method comprises the following steps of reacting peracetyl-protected glucose and potassium thioacetate in an organic solvent at the temperature of between normal temperature and 50 DEG C under the catalysis of boron trifluoride diethyl ether for 4-8 hours to obtain peracetyl-protected 1-thioglucose; and dissolving the prepared peracetyl-protected 1-thioglucose in dimethylformamide, and removing thioacetyl by using hydrazine hydrate to obtain peracetyl-protected glucose 1-mercaptan. The peracetyl-protected glucose 1-mercaptan can be used for further preparing auronofen and gliclazide thioglycoside analogues. The method disclosed by the invention is mild in reaction condition, simple and convenient to operate, low in synthesis cost, relatively green and high inyield, the auronofen is a medicine for treating rheumatic arthritis, and the gliflozin thioglycoside analogue is a potential medicine for treating type 2 diabetes mellitus.

Description

technical field [0001] The invention belongs to the technical field of medicine and sugar chemical synthesis, and in particular relates to a preparation method and application of fully acyl-protected 1-thioglucose and glucose 1-thiol. Background technique [0002] Auranofin is an oral drug that has been on the market for many years and can be used to treat rheumatoid arthritis. Recent studies have shown that it also has anti-inflammatory and potential anti-tumor activities. It is usually prepared from peracetyl-protected glucose 1-thiol, triethylphosphine and potassium chloroaurate. Gliflozin drugs are drugs developed from bark bark glycosides (phlorizin) for the treatment of type 2 diabetes. They are both inhibitors of the glucose cotransporter (SGLT-2), as follows: [0003] [0004] Ggliflozin SGLT-2 Inhibitors [0005] Since bark glycoside is an oxygen glycoside, it is easily hydrolyzed by β-glucosidase, so it cannot be used as a drug. Ggliflozin drugs are all car...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H15/26C07H15/203C07H1/00C07H23/00A61P19/02A61P29/00A61P3/10C07H13/04
CPCC07H15/26C07H15/203C07H1/00C07H23/00A61P19/02A61P29/00A61P3/10C07H13/04
Inventor 董海冯广京
Owner HUAZHONG UNIV OF SCI & TECH
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