Synthesis method of compounds of 5-benzoyl-1, 4-naphthaquinone with similar gossypol effect

Abstract

The invention discloses a practical synthesis method of compounds of 5-benzoyl-1, 4-naphthaquinone with a similar gossypol effect. The practical synthesis method comprises the steps that: a) malonic acid and acrolein take condensation reaction to obtain a compound of pentadienoic acid shown in the formula I; b) the compound shown in the formula I takes reaction with p-benzoquinone to obtain a compound of cis-5, 8-diketone-1,4,6,7,9,10-hexahydronaphthalene-beta-carboxylic acid shown in the formula II; c) the compound shown in the formula II is subjected to methylation to obtain a compound of 5,8-dimethoxy-1,4-dihydronaphthalene-1-carboxylic acid-methyl ester shown in the formula III; d) the compound shown in the formula III takes dehydro-aromatization reaction to obtain a compound of 5,8-dimethoxy naphthoate shown in the formula IV; e) the compound shown in the formula IV is hydrolyzed to obtain a compound of 5,8-dimethoxy naphthoyl naphthoic acid shown in the formula V; f) the compound shown in the formula V is subjected to chlorination to obtain a compound of 5,8-dimethoxy naphthoyl chloride shown in the formula VI; g) the compound shown in the formula VI and benzene are subjected to Friedel-Crafts acidylation to obtain a compound of 5-benzoyl-1,4-dimethoxy naphthalene shown in the formula VII; and h) the compound shown in the formula VII is oxidized to obtain a compound of 5-benzoyl-1,4-naphthoquinone shown in the formula VIII.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, in particular to a method for synthesizing 5-benzoyl-1,4-naphthoquinone compounds with gossypol-like effects Background technique [0002] Gossypol (gossypol) is a yellow polyphenolic toxic substance in cotton plants, and its chemical structure is 8,8'-dihydroxyaldehyde-1,1',6,6',7,7'-hexahydroxy -5,5'-diisopropyl-3-3'-dimethyl-2,2'-binaphthyl, with a molecular weight of 518.54. [0003] In the 1960s, Chinese scientists first discovered that gossypol had a definite anti-spermogenic effect, which once triggered an upsurge in research on the anti-fertility effect of gossypol. However, taking gossypol for a long time can cause hypokalemia and irreversible infertility. The above two toxic and side effects greatly limit the promotion and application of gossypol as a male birth control drug, and also interrupt most of the research on gossypol . In addition to having significant male anti-fertility...

AI Technical Summary

Problems solved by technology

The actual yield of the oxidation step of the method is very low and there are many by-products, and the CrO used in the reaction 3 It has strong toxicity, troublesome post-treatment, and produces a large amount of waste water, which is not conducive to large-scale preparation

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