Preparation method of hydrocortisone acetate or analogue thereof

Abstract

The invention relates to a preparation method of hydrocortisone acetate or an analogue thereof. Hydrocortisone acetate or the analogue thereof has a structural formula represented as a formula VIII. According to the invention, a compound I is subject to an oxidation reaction, a carbonyl protection reaction, a reduction and hydrolysis reaction, a cyano substitution reaction, a silicon alkyloxy protection reaction, an intramolecular nucleophilic substitution reaction, and a substitution reaction, such that hydrocortisone acetate or the analogue thereof is prepared. The initial raw materials areeasy to obtain, and the yield is high and stable. The compound I is represented by a formula I, wherein R is H or alkyl.

Description

technical field

[0001] The invention relates to a preparation method of hydrocortisone acetate or its analogs. Background technique

[0002] Hydrocortisone, as the most produced variety of steroidal corticosteroids, is widely used in the treatment of adrenal insufficiency and autoimmune diseases. my country's steroid drug and its intermediate industry has reached a certain scale, and it has become the largest exporter of hydrocortisone and prednisolone in the world. Currently, hydrocortisone is mainly synthesized by biological fermentation and chemical synthesis, which have the problems of low yield and high cost.

[0003] The difficulty in the synthesis of hydrocortisone lies in the introduction of 11β-hydroxyl. Because there is no active functional group around the C-11 position, conventional chemical methods are difficult to oxidize inactive carbon-hydrogen bonds, but biocatalytic methods can oxidize it stereoselectively. The effective strains are Rhizopus niger and Ab...

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