Azasteroids derived from fusidic acid

Abstract

The Beckmann rearrangement pathway of the (E)-11-oxime 6, derived from fusidic acid, one of the uncommon 9β-steroids with ring B constrained in a boat conformation, was investigated. It was found that 6 was converted into methyl 3-O-acetyl-11-aza-11a-homo-11a-oxo-24,25-dihydrofusidate 7, the ‘normal’ product of rearrangement, when treated with toluene-p-sulfonyl chloride in pyridine. The structure and stereochemistry of 7 was determined by X-ray crystallography. The absolute configuration of fusidic acid was confirmed. The Beckmann rearrangement of the oxime derivatives of 3- and 17-oxo-9β-steroids derived from fusidic acid was also investigated. In general, with the exception of the (E)-oxime of 17-oxotriacetate 13b, which resulted in a complex mixture of products, none of which predominated, all the oximes gave the normal Beckmann rearrangement products.