Atovaquone synthesis technology

Abstract

The invention discloses an atovaquone synthesis technology. The atovaquone synthesis technology comprises that in the presence of a silver nitrate catalyst, 2-ethoxy-1, 4-naphthoquinone and 4-(4-chlorophenyl)cyclohexyl-1-formic acid as raw materials are dissolved in an acetonitrile solvent, then the solution is added into a reactor and is heated along with stirring until reflux so that the reaction system undergoes a reaction, wherein in reflux, an ammonium persulfate aqueous solution is dropwisely added into the reaction system and the mole amount of the ammonium persulfate is 3-5 times that of 2-ethoxy-1, 4-naphthoquinone, after the reaction, the product is cooled and forms crystals, the crystals are filtered and are dissolved through trichloromethane, the solution is filtered, the filtrate is collected and is subjected to reduced pressure distillation so that trichloromethane is removed, and the solution is subjected to acetonitrile recrystallization so that atovaquone yellow acicular crystals are obtained. The atovaquone synthesis technology only needs one step, saves a synthesis cost, has a high yield and can produce high-purity atovaquone.

Description

technical field [0001] The invention belongs to the technical field of drug synthesis, and in particular relates to a synthesis process of atovaquone. Background technique [0002] Atovaquone is a hydroxy 1,4-naphthoquinoline, a homologue of coenzyme Q, which has activity against several protozoa. For Plasmodium, its action site is the binding point of cytochrome bcl (binding point III), which can reversibly combine with the 11500Da molecular group on the polypeptide. Dihydrolactate dehydrogenase is an important enzyme in pyridine biosynthesis. It connects mitochondria for electron transfer through coenzyme Q, so it can prevent pyridine synthesis by inhibiting electron transfer. In the current synthesis process of the antineoplastic drug melphalan, the process is not easy to implement, the resulting atovaquone product has low purity, low single-pass conversion rate of reactants, complex production process, low production efficiency and high cost, which is not suitable for...

AI Technical Summary

Problems solved by technology

In the current synthesis process of the antineoplastic drug melphalan, the process is not easy to implement, the resulting atovaquone product has low purity, low single-pass conversion rate of reactants, complex production process, low production efficiency and high cost, which is not suitable for mass production