Synthesis and Biological Evaluation of Some A,D-Ring Modified 16,17-Secoandrostane Derivatives

Abstract

Starting from 3β-hydroxy-17-oxo-16,17-secoandrost-5-ene-16-nitrile ( 1 ), the new 16,17-secoandrostane derivatives 2 - 11 were synthesized. Protection of the 17-oxo function of compound 1 with ethylene glycol yielded compounds 2 and 3 . The Oppenauer oxidation of 2 or oxidation with H 2 O 2 in alkaline conditions gave the respective compounds 4 and 10. Epoxidation of compound 4 yielded a mixture of 4α,5α- and 4β,5β-epoxides 5 and 6 and a mixture of 4α,5α- and 4β,5β-epoxy-carboxamides 7 and 8 . Opening of the oxirane ring of a mixture of compounds 5 and 6 with formic acid afforded the 4-hydroxy derivative 9 . Anti-aromatase activity and in vitro cytotoxicity for three tumor cell lines (human breast adenocarcinoma ER+, MCF-7 as well as human breast adenocarcinoma ER-, MDA-MB-231, and prostate cancer, PC3) of selected compounds were evaluated. Compounds 2 , 4 , 9 , and 10 showed a strong cytotoxicity for PC3 cells.