Synthesis method of 1, 1 '-deoxygossypol

Abstract

The invention discloses a systhesiz method of 1, 1 '-deoxygossypol . The method comprises the following steps: 1, taking gossypol acetate I as a starting material, taking gossypol acetate I as a starting material, and removing aldehyde groups to obtain apogossypol II; 2, acetylating the aspogossypol II to obtain aspogossypol III; 3, selectively removing acetyl of the aspogossypol III to obtain an intermediate IV; 4, protecting phenolic hydroxyl of the intermediate IV to obtain an intermediate V; 5, removing acetyl from the intermediate V to obtain an intermediate VI; 6, protecting phenolic hydroxyl of the intermediate VI to obtain an intermediate VII; 7, reducing the protected phenolic hydroxyl group of the VII of the intermediate to obtain a 1, 1'- deoxygossypol precursor VIII; and 8, removing a methoxy group of the 1, 1'- deoxygossypol precursor VIII to obtain a target product 1, 1 '-deoxygossypol . Reaction raw materials are cheap and easy to obtain, synthesis process steps are fewer, the total yield is as high as 45%, reaction conditions are mild, and safety is high. The method is simple in technological process and post-treatment, easy to operate and good in industrial prospect.

Description

technical field [0001] The invention belongs to the field of organic synthesis and relates to a method for synthesizing 1,1'-deoxygossypol. Background technique [0002] Gossypol is a yellow polyphenol compound, which has various biological activities such as anti-tumor and anti-virus, and is a very promising natural compound. [0003] 1,1'-Deoxygossypol was found to have anti-HIV activity. At present, there is only one report on the synthesis of 1,1'-deoxygossypol, which is a total synthesis method (reference: J.Med.Chem.1995, 38, 2427-2432). The reaction scheme is shown below. Starting from 1-bromo-2-isopropyl-3,4-dimethoxybenzene A, after 9 steps of Grignard, cyclization, and coupling reactions, the total yield is 16.9%. 1,1'-Deoxygossypol. Although this route can successfully obtain the target product 1,1'-deoxygossypol, there are many defects: [0004] 1) The starting material 1-bromo-2-isopropyl-3,4-dimethoxybenzene (CAS: 77256-01-0, 1g / 2325 yuan) is scarce and dif...

AI Technical Summary

Problems solved by technology

[0004] 1) The starting material 1-bromo-2-isopropyl-3,4-dimethoxybenzene (CAS: 77256-01-0, 1g / 2325 yuan) is scarce and difficult to synthesize, so the price is particularly high, not economy;

[0005] 2) The synthetic route is 9 steps, the total yield is 16.9%, the steps are cumbersome, and the total yield is low;

[0006] 3) The reagents used in literature reports include H 2 , n-BuLi, Br 2 etc. are flammable, explosive, and highly toxic items, and there are potential safety hazards. The use of n-BuLi needs to be controlled at -78°C, and the requirements are relatively stringent.

[0008] Combined with the above analysis, the currently disclosed synthesis method of 1,1'-deoxygossypol cannot meet the needs of research and production, and a new method that can adapt to industrial production is urgently needed

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