Method for chemically synthesising gastrodin

Abstract

The invention discloses a method for chemically synthesising gastrodin, comprising the following steps of: in the presence of a molecular sieve, under the catalysis of Lewis acid, and performing glycosylation reaction on pent-acetyl-b-D-glucose and p-cresol in an organic solvent with to generate 4-methylphenyl-2,3,4,6-O-tetra-acetyl-b-D-glucopyranoside; then preparing 4-halomethylphenyl-2,3,4,6-O-tetra-acetyl-b-D-glucopyranoside from 4-methylphenyl-2,3,4,6-O-tetra-acetyl-b-D-glucopyranoside and N-halosuccinimide in the presence of an initiator, and then reacting 4-halomethylphenyl-2,3,4,6-O-tetra-acetyl-b-D-glucopyranoside with the mixed solution of glacial acetic acid and tertiary amine to obtain 4-acetoxylmethylphenyl-2,3,4,6-O-tetra-acetyl-b-D-glucopyranoside; and finally removing the acetyl protecting group from the 4-acetoxylmethylphenyl-2,3,4,6-O-tetra-acetyl-b-D-glucopyranoside in an alkaline condition to obtain gastrodin. Compared with the traditional method, the method disclosed by the invention has easily available raw materials, and is short in reaction time, capable of preparing the reaction product in each step via recrystallization, simple, and more suitable for industrialized production for gastrodin.

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, namely 4-hydroxymethylphenyl-β-D-glucopyranoside, is the main active ingredient of Gastrodia elata Blume, which has sedative, anticonvulsant, anti-inflammatory and immune-enhancing effects. It is widely used in the auxiliary 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. Because the content of gastrodin in Gastrodia elata is very low (about 0.1%), there are problems such as high extraction cost, heavy workload, difficult preparation of high-purity samples and unfavorable resource protection by using plant extraction method to obtain gastr...

AI Technical Summary

Problems solved by technology

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 Chemie Sinica, 1980, 32(2), 162-166]. Large red phosphorus and bromine have serious three waste treatment problems, which are 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 used by my country to synthesize gastrodin Adopted by major manufacturers of APIs

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], the synthesis method still uses red phosphorus and bromine , just change the potassium borohydride reduction step to Raney nickel catalytic hydrogenation, although the improvement of this synthesis method has increased the total yield (31%), but the practical application is of little significance, and it also faces the problem of introducing heavy metals

In 2004, Dai Xiaochang et al. reported the chemical synthesis process of gastrodin and its similar phenolic glycosides [Dai Xiaochang, Peng Xiao, Wu Songfu, Yang Wansong, Mao Yu, The chemical synthesis process of gastrodin and its similar phenolic glycosides, Journal of Yunnan University for Nationalities (Natural Science Edition), 2004, 3(2), 83-85], this process only uses phosphorus tribromide to replace the red phosphorus and bromine used in the above two synthetic methods, and there is no substantial change in addition, Also facing the problems of environmental pollution, low yield and high cost

As mentioned earlier, the preparation of tetraacetylbromoglucose needs to use red phosphorus and bromine or phosphorus tribromide, thereby causing serious harm and pollution to producers and the environment; and tetraacetylbromoglucose itself is unstable and inconvenient Production storage and use, so the yield of the subsequent glycosylation reaction under alkaline and phase transfer catalysis conditions is low (35-46.5%), and the resulting glycosylation product 4-formylphenyl-2,3 ,The formyl group in 4,6-O-tetraacetyl-β-D-glucopyranoside is reduced to a hydroxymethyl group. In the reduction process, potassium borohydride or Raney nickel is used to catalyze hydrogenation. The price of potassium borohydride Therefore, the production cost is high, and Raney nickel catalytic hydrogenation reduction also faces the problem of introducing heavy metals into the product

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