Synthesis method of anti-influenza and avian influenza virus resistant medicine peramivir

Abstract

The invention belongs to the synthesis technical field of organic medicine, and discloses a synthesis method of anti-influenza and avian influenza virus resistant medicine peramivir, which is characterized by adopting (1R, 4S)-2-azabicyclo[2.2.1]hept-5-en-3-one as a raw material and by comprising the following steps: step I: catalyzing, loop-opening and amino protection; step II: 1,3-dipolarcycloaddition; step II: sodium borohydride and nickel chloride hexahydrate reduction and acetylization; and step IV: amino protection removal, and chloroformamidine hydrochloride is adopted as reaction agent to generate guanidyl and hydrolysis methyl ester to prepare peramivir. The sodium borhydride and the nickelous chloride reduction system is used for substituting the expensive platinum dioxide to be used as reducing agent during the hydrogenation reduction process, and the self-produced chloroformamidine hydrochloride is used during the process for feeding the guanidyl reagent, so the cost is reduced, and the operation procedures are simplified. The synthesis method has short reaction routine and moderate reaction condition, is simple and convenient to operate, has low cost, and is suitable for the industrialized production.

Description

technical field [0001] The invention belongs to the technical field of organic medicine synthesis. Specifically, the invention relates to a synthesis method of an anti-influenza and avian influenza virus drug and an influenza virus neuraminidase inhibitor peramivir. Background technique [0002] Influenza, referred to as influenza for short, is an acute respiratory disease caused by influenza virus, which has the characteristics of strong infectivity, fast transmission speed, high morbidity and mortality. [0003] The structure of influenza virus is actually not complicated. It is a fat globule with eight RNA strands inside. There are many important proteins on the surface of the globule. They are "nailed" on the surface like "nails". figure 1 . These "nails" are divided into two categories, one is hemagglutinin (HA), which is used for virus infection of host cells, and the other is neuraminidase (NA), which is responsible for cutting off host cells and determines the effic...

AI Technical Summary

Problems solved by technology

[0011] The synthetic route is to use (1R, 4S)-2-azabicyclo[2.2.1]hept-5-en-3-one as raw material, through nine-step reaction to synthesize peramivir, the route is longer and the yield low rate

In the cycloaddition process, highly toxic benzene and phenyl isocyanate are used; and in the hydrogenation reduction process, the relatively expensive platinum dioxide is used as a catalyst, which requires hydrogen reduction, and the requirements for safe operation are relatively high; The highly toxic mercuric chloride is used in the process of guanidinylation reagent, which causes environmental pollution and is not suitable for industrial production

[0012] The drug has not yet been approved for marketing in China

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