Disaccharide intermediate and synthesis method thereof

Patent metadata

Field	Value
Publication number	US-10287309-B2
Application number	US-201415036390-A
Country	US
Kind code	B2
Filing date	Apr 28, 2014
Priority date	Nov 14, 2013
Publication date	May 14, 2019
Grant date	May 14, 2019

Abstract

The present invention relates to a disaccharide intermediate and a synthesis method thereof, relates to the chemical pharmaceutical field, and more specifically relates to a method for preparing a disaccharide segment of a key intermediate for chemically synthesizing heparin and heparinoid compounds. Disclosed are a new disaccharide intermediate and three methods for synthesizing the disaccharide intermediate, that is, compounds of a formula (4) and glucopyranose protected by different anomeric carbon are made to react in the presence of an active agent, to obtain the disaccharide intermediate. According to the technical solutions of the present invention, synthetic raw materials are easy to obtain, have a mild reaction condition, and are suitable for industrialized production.

First claim

The invention claimed is:

1. A process for preparing a compound of formula (2), comprising a step of glycosylation reaction between a compound of formula (3) and a compound of formula (4) in the presence of an active agent:

wherein:
R is an alkanoyl group or an aroyl group, and R in the same formula represents the same groups; and
the active agent is selected from one or more of boron trifluoride-diethyl ether complex, trimethylsilyl triflate, triethylsilyl triflate, t-butyl dimethylsilyl triflate, and trifluoromethanesulfonic acid.

2. The process according to claim 1 , wherein the anomeric carbon of the compound of formula (3) has a stereo-configuration of α or β or a mixture thereof.

3. The process according to claim 1 , wherein the glycosylation reaction is carried out in the presence of a solvent.

4. The process according to claim 1 , wherein R is an acetyl group or a benzoyl group.

5. The process according to claim 1 , wherein R is benzoyl.

6. The process according to claim 3 , wherein the solvent is ethyl acetate, methyl acetate, N,N-dimethylformamide, ethyl ether, methyl t-butyl ether, tetrahydrofuran, 2-methyl tetrahydrofuran, dioxane, acetonitrile, nitromethane, dichloromethane, 1,2-dichloroethane, or toluene, or a mixture thereof.

7. The process according to claim 1 , wherein R is an acetyl group.

Assignees

• Zhejiang Hisun Pharm Co Ltd

Inventors

• Guo Yanghui
• Zhou Junhui
• Cai Qingfeng
• Wei Hegeng
• Bai Hua
• Long Fei
• Zhang Yue
• Wu Yingqiu

Classifications

• C07H3/10

  Anhydrosugars, e.g. epoxides · CPC title

• C07H1/00 Primary

  Processes for the preparation of sugar derivatives · CPC title

• C07H13/04

  having the esterifying carboxyl radicals attached to acyclic carbon atoms · CPC title

• C07H13/08

  having the esterifying carboxyl radicals directly attached to carbocyclic rings · CPC title

• C07H17/04

  Heterocyclic radicals containing only oxygen as ring hetero atoms · CPC title