Synthesis and biological activity of some 17a-substituted homolactones of androst-5-ene derivatives

Abstract

Some new 17a-homolactones were prepared from 3β-hydroxy-16- (hydroxyimino)androst-5-en-17-one (1) as a starting compound, which was transformed first to the corresponding 17α-phenyl and 17α-benzyl derivatives 2 and 3. The structure of compound 3 was confirmed by X-ray structure analysis. Beckmann fragmentation of compounds 2 and 3 yielded 16,17-seco-cyano ketones 4-7, whose reduction with NaBH4 gave 16,17-seco-cyano alcohols 8-11, whereby the structure of compound 7 was established by X-ray structural analysis. Compounds 8-11 served as the starting compounds for obtaining lactones 12 and 13 in a reaction with potassium hydroxide in ethylene glycol. One-pot procedures were also developed for preparing 17a-homolactones 12, 13 and 16 from the hydroxyimino alcohols 2, 3 and 14. Compounds 12 and 13 showed an inhibitory activity against the enzyme aromatase (63 and 59%, respectively).