SYNTHESIS OF (17R) AND 17S)-17-HYDROXY-14,15-SECOANDROST-4-EN-16-YN-3-ONE AND THE X-RAY CRYSTAL-STRUCTURE OF THE (17S)-DIASTEREOMER

R,S)-17-Hydroxy-14,15-secoandrost-4-en-15-yn-3-one has been shown prev iously to be a mechanism-based inactivator of rat liver 3 alpha-hydrox ysteroid dehydrogenase. This manuscript describes the synthesis of thi s diastereomeric 14,15-secosteroid from [2S-2 alpha,4a alpha,4b beta,1 0a beta)]-1,2,3,4a,4b, 7,9, hydro-2,4b-dimethyl-7-oxo-2-phenanthreneca rboxylic acid methyl ester. The separation of this diastereomeric 14,1 5-secosteroid into (17R)- and 17S)-17-hydroxy-14,15-secoandrost-4-en-1 5-yn-3-one was accomplished by HPLC separation of the 4-methylphenyl)s ulphonyl]-2-pyrrolidinecarboxylate derivatives on a silica column. The crystal structure of 17S)-17-hydroxy-14,15-secoandrost-4-en-15-yn-3-o ne was then solved by X-ray diffraction analysis to establish unambigu ously the absolute configuration of the diastereomeric 14,15-secostero id.