Method for preparing spirolactone by chemical-enzymatic method

Abstract

The invention discloses a method for preparing spirolactone by a chemical-enzyme method, and belongs to the technical field of organic synthesis. According to the method for preparing the spirolactone through the chemical-enzymatic method, 4AD serves as a raw material, and the spirolactone is obtained through enol etherification, epoxidation, lactonization, enzymatic dehydrogenation and sulfo-reaction. The enzymatic dehydrogenation method adopted by the spirolactone synthesis process route is good in specificity, mild in condition, free of special equipment and high in catalytic rate; the reaction product in each step involved in the method is easy to purify, the total mass yield of the final product is higher than 92%, and the HPLC purity is higher than 99.8%; the method is low in cost and suitable for industrial large-scale production, and has good economic benefits.

Description

【Technical field】 [0001] The invention relates to the technical field of organic synthesis, in particular to a method for preparing spironolactone, in particular to a method for preparing spironolactone by combining chemical and enzymatic methods. 【Background technique】 [0002] Spironolactone is a weak potassium-sparing diuretic, also known as spironolactone and spironolactone. It is a white or off-white fine crystalline powder with a slight bitter taste, odorless or a slight thiol odor. Easily soluble in chloroform, insoluble in water, soluble in ethanol, soluble in benzene or ethyl acetate. The chemical structure is similar to that of aldosterone, which can compete with aldosterone for the aldosterone receptor in the cytoplasm of the distal convoluted tubule and collecting duct, affecting the binding of aldosterone to the receptor, thus hindering the synthesis of aldosterone-induced protein, thereby inhibiting the K+-Na+ exchange and reducing the excretion of potassium ,...

AI Technical Summary

Problems solved by technology

The synthesis method has harsh reaction conditions, high requirements on equipment, difficult operation, many steps, expensive reagents, low total yield and high cost

[0005] The second is to use androstenedione as the starting material, and obtain the lactone compound through etherification, epoxidation, and lactonization, and then through bromination, dehydrobromination, and then addition reaction to obtain; the synthesis The method uses a brominating agent in the process of bromination and debromination, which is not friendly to the environment, and high temperature debromination is used for debromination, with large impurities and low yield

There are also reports in the literature that chlorobenzoquinone is used for dehydrogenation when the 3-position keto group or enol is etherified, but chlorobenzoquinone and by-product tetrachloroquinone are difficult to handle, causing a lot of pollution

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