Gastrodin chemical synthesis method suitable for industrialization

Abstract

The invention discloses a gastrodin chemical synthesis method. The method comprises the steps as follows: under Lewis acid catalysis, D-glucose reacts with acetic oxide, pentacetyl-D-glucose is obtained and not subjected to separation and purification; the pentacetyl-D-glucose and the p-cresol are catalyzed by Lewis acid and subjected to a glycosylation reaction directly in an organic solvent, so that 4-methylphenyl 2,3,4,6-O-tetracetyl-b-D-glucopyranoside is generated; then the 4-methylphenyl-2,3,4,6-O-tetracetyl-b-D-glucopyranoside reacts with 1,3-dibromo-5,5-dimethylhydantoin under the action of an initiator or in solar radiation, so that 4-bromomethyl-2,3,4,6-0-tetracetyl-b-D-glucopyranoside is obtained; then under the alkalescence condition, 4-bromomethyl-2,3,4,6-0-tetracetyl-b-D-glucopyranoside is hydrolyzed selectively, so that 4- Hydroxymethyl phenyl-2,3,4,6-O-tetracetyl-b-D-glucopyranoside is obtained; and finally an acetyl protecting group is removed from a methyl alcohol-sodium methoxide system, so that the gastrodin is obtained. Compared with a conventional method, the gastrodin chemical synthesis method has the advantages as follows: raw materials are easy to obtain, the cost is low, reaction products in all steps can be prepared through recrystallization, the process is simple, the reaction period is short, the yield is high, and the method is more suitable for preparing the gastrodin in large scale.

Description

technical field [0001] The invention belongs to the field of pharmaceutical chemical industry, in particular to a method for chemically synthesizing gastrodin. Background technique [0002] Gastrodin, whose chemical name is 4-hydroxymethylphenyl-β-D-glucopyranoside, is the main active ingredient of the orchid plant Gastrodia elata, which has sedative, anticonvulsant, anti-inflammatory and immune-enhancing effects. It is widely used in the adjuvant treatment of vertigo, headache (neurasthenia and neurasthenia syndrome, vascular headache, tension headache, brain trauma syndrome, migraine, etc.) and epilepsy. [0003] At present, gastrodin raw materials for clinical application mainly come from plant extraction and chemical synthesis. Since the content of gastrodin in Gastrodia elata is extremely low (about 0.1%), there are problems such as high extraction cost, heavy workload, and resource limitation in obtaining gastrodin by plant extraction. To develop a method for large-sc...

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Problems solved by technology

At present, there are few literature reports on the biosynthesis of gastrodin, mainly focusing on cell culture and microbial transformation [Cai Jie, Jia Yi, Hua Yanan, Li Nan, Establishment of biosynthetic gastrodin transformation system in ginseng hairy roots, Plant Resources and Environmental Science, 2005, 14 (2), 29-31; Gong Jiashun, Ma Weipeng, Pu Junxue, Xu Shuguan, Zheng Shuangqing, Xiao Chunjie, Baihua Datura suspension culture cells transform p-hydroxybenzaldehyde to gastrodin, Acta Pharmaceutica Sinica, 2006 , 41(10), 963-966; Zhu Hongli, Song Jirong, Huang Jianxin, Zhang Jia, Ma Zhenyu, Yang Mingyan, Synthesis of Gastrodin by Microbial Transformation, Acta Pharmaceutica Sinica, 2006, 41(11), 1074-1077], but all biological The methods of synthesizing gastrodin are all in the stage of laboratory exploration, and it will take time to realize large-scale industrial production

[0005] The chemical synthesis of gastrodin began in the 1980s. In 1980, Zhou Jun and others completed the chemical synthesis of gastrodin for the first time [Zhou Jun, Yang Yanbin, Yang Chongren, Chemical Research on Gastrodin II, Acta Chemical Journal, 1980, 32 (2), 162-166], this synthetic route uses a large amount of toxic red phosphorus and bromine, which has serious waste treatment problems, which is not conducive to production safety and environmental safety, and the total yield is low (24%), and the production cost is high , but this synthetic route is still adopted by the main manufacturers of synthetic gastrodin raw materials in my country

In 1984, Pang Qijie and others reported an improved method for the synthesis of gastrodin [Pang Qijie, Zhong Yuguo, Improvement of the synthesis method of gastrodin, Pharmaceutical Industry, 1984, (3), 3-4], which still uses red phosphorus and bromine ,

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