A kind of synthetic method of salidroside and intermediate compound thereof

Abstract

The invention discloses a synthesis method for salidroside and an intermediate compound obtained in the synthesis method. The synthesis method comprises the following steps: (1) under the catalytic action of Lewis acid, carrying out a reaction between hydroxyl-protected benzyl carbinol and acyl-protected glucose ester to obtain the intermediate compound shown in formula (IV); (2) putting the intermediate compound shown in formula (IV) in C1-C4 alkanol, removing acyl protecting groups in the presence of alkali, and carrying out drying to obtain salidroside shown in the formula (I). The detailed definitions of substituent groups in formula (III) and formula (IV) are shown in the description. The synthesis method has the advantages of being simple to operate, mild in condition, high in yield and easy for industrialization.

Description

technical field [0001] The invention belongs to the field of pharmaceutical chemical synthesis, and relates to a synthesis method of natural products, more specifically, to a synthesis method of salidroside and an intermediate compound thereof. Background technique [0002] Salidroside is the active ingredient of Rhodiola rosea, which has the functions of protecting the cardiovascular system, protecting the central nervous system, anti-virus, anti-tumor, anti-aging, anti-radiation, anti-hypoxia, anti-injury, promoting blood circulation and removing blood stasis and improving Immunological function and many other significant effects. Rhodiola is a perennial herb or subshrub of Crassulaceae. The whole herb can be used as medicine. Its stems, roots, and flower extracts are all red in color. The content of salidroside in the medium is low (1.0%), so that the cost of extracting salidroside from Rhodiola rosea is high, the yield is low and the purity is poor. [0003] [0004...

AI Technical Summary

Problems solved by technology

[0005] Li Guoqing et al. (Li Guoqing, Li Zhan. Improvement of the synthetic method of salidroside [J], Chinese Journal of Medicinal Chemistry, 1996, 6 (2): 136-137) reported a synthetic method of salidroside, using hydroxybenzene Ethyl acetate is used as a raw material to synthesize salidroside through the steps of benzyl protection, lithium aluminum hydride reduction, glycoside formation with bromoacetylglucose, and deprotection. The reaction process requires anhydrous operation, and a large amount of aluminum is produced during post-treatment. Salt, causing environmental pollution, lower yield and higher cost.

[0006] Zhang Sanqi et al. (Zhang Sanqi, Shang Gangwei, Li Zhongjun, etc. A new approach to the synthesis of salidroside [J], Chinese Journal of Medicinal Chemistry, 1997, 7(4): 256-257) reported the synthesis of a salidroside method, using p-bromophenol to synthesize salidroside through the steps of allylation, epoxidation, glycosidation and deprotection. This reaction uses the catalyst silver nitrate, which has high cost and has caused heavy metal pollution

[0007] Zhang Lianji (Zhang Lianji, Li Xuemei, Tian Guanrong. Synthesis of salidroside [J]. Yanbian University Journal, 2002, 28 (2): 97-98) reported a synthetic method of salidroside, using hydroxyphenylacetic acid as The raw material is synthesized into salidroside through seven steps. This reaction has many steps, consumes too much time and cost, and the yield is not high. The flammable palladium carbon and lithium aluminum hydride used in the reaction process

[0008] Deng Mei (Deng Mei, Wu Zhengang, Liu Xueying, et al. Synthesis of salidroside and its analogs [J]. Journal of Fourth Military Medical University, 2007, 28(16): 1501-1502) reported a rhodiola The synthetic method of glucoside uses p-hydroxyphenylacetic acid as raw material to synthesize salidroside through acetylation, sodium borohydride reduction, glycosidation and alcoholization reactions. This process also has more steps, lower yield and poorer purity

[0009] Chinese patent application CN201110184190.3 reports a synthesis method of salidroside, using Lewis acid as a catalyst, phenethyl alcohol with acyl-protected phenolic hydroxyl as a glycosylation acceptor, and D-pentaacetylglucose as a glycosylation donor. Carry out glycosylation reaction, obtain 1-[2-(4-acyloxyphenyl) ethyl]-2,3,4,6-O-tetraacetyloxy-acetyloxyglucopyranoside, then in Salidroside is obtained by removing the protection of the acyloxy group under alkaline conditions. This method reacts slowly under the catalysis of Lewis acid, and the acetyl protecting group on the sugar is easy to undergo esterification reaction with the acyl-protected phenolic hydroxyphenylethanol, resulting in glycosidation difficult to react

Since the method does not protect the phenolic hydroxyl group, the selectivity of the glycosylation reaction is very poor, and the carbonyl group, the phenolic hydroxyl group, and the alcoholic hydroxyl group all undergo glycosylation reactions.

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