Synthesis and Biological Activity of Some 17a‐Substituted Homolactones of Androst‐5‐ene Derivatives.

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 NaBH 4 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).