Method of synthesizing 2alpha,3alpha-epoxy-16alpha-bromo-5alpha-androsterone-17-one

Abstract

The invention discloses a making method of 2 alpha, 3 alpha-epoxy-16 alpha-bromine-5 alpha-androstane-17-ketone as intermediate of steroidal muscular relaxation drug, which comprises the following steps: dissolving epiandrosterone in the benzene; adding catalyst; stirring; heating; refluxing 8-12h; preparing 5 alpha-androst-2-olefin-17-ketone; reacting the 5 alpha-androst-2-olefin-17-ketone and copper bromide in the carbinol to produce 16 alpha-bromine-5 alpha-androst-2-olefin-17-ketone; reacting the 16 alpha-bromine-5 alpha-androst-2-olefin-17-ketone and m-perbenzoic acid in the composite solvent of water and dichloromethane; producing the product through eliminating, bromizing and epoxidising.

Description

Technical field: [0001] The invention relates to a preparation method of a steroidal muscle relaxant intermediate, belonging to the technical field of medicinal chemistry. technical background: [0002] Neuromuscular blocking drugs are also called muscle relaxants, or muscle relaxants for short. It was first used in clinical anesthesia in 1942. Before the 1980s, the muscle relaxants commonly used in clinical practice mainly included succinylcholine, tubocurarine, dimethyltubocurarine, triiodoquaternary ammonium phenol, etc. However, these drugs all have certain cardiovascular side effects, which are generally due to stimulation or inhibition of the peripheral autonomic nervous system; or the release of histamine and other vasoactive substances from vascular mast cells; or following the depolarization of the motor end plate, serum Caused by elevated potassium levels. Later, a large number of new muscle relaxants have been developed and used in clinical anesthesia, and their...

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Problems solved by technology

[0016] But this route has following three shortcoming: 1. step 1 is reversible reaction, is difficult to carry out to the end, always has a certain amount of raw material to exist, and product is unstable, returns to raw material structure easily, so extremely difficult to purify, yield is very low ; 2. the yield reported in the second step has only 55%, so that the total yield of the two-step reaction is very low, relatively making the production cost become very high; 3. enol acetylation reagent isopropenyl acetate can only be Rely on imports, very expensive

But generally speaking, this synthetic route is still long, and the yield of each step is not good, and the loss in the purification process is serious, resulting in a small increase in the overall yield compared with the previous method.

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