Collect. Czech. Chem. Commun.
2005, 70, 1387-1396
https://doi.org/10.1135/cccc20051387
Synthesis and Biological Activity of Some 17a-Substituted Homolactones of Androst-5-ene Derivatives
Katarina M. Penov Gašia,*, Srdjan Z. Stojanovića, Marija N. Sakača, Evgenija A. Djurendića, János J. Csanádia, Dora Molnar-Gabora, Dušan Lazarb and Radmila M. Kovačevićc
a Department of Chemistry, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia and Montenegro
b Department of Physics, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 4, 21000 Novi Sad, Serbia and Montenegro
c Department of Biology, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 2, 21000 Novi Sad, Serbia and Montenegro
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).
Keywords: Steroids; D-homoandrostene derivatives; Steroidal lactones; Aromatase inhibitors; X-Ray analysis; Oximes; D-ring cleavage.
References: 11 live references.
