Synthesis of (17R)- and (17S)-17-hydroxy-14, 15-secoandrost-4-en-15-yn-3-one and the X-ray crystal structure of the (17S)-diastereomer

(17R,S)-17-Hydroxy-14,15-secoandrost-4-en-15-yn-3-one has been shown previously to be a mechanism-based inactivator of rat liver 3α-hydroxysteroid dehydrogenase. This manuscript describes the synthesis of this diastereomeric 14,15-secosteroid from [2S-(2α,4aα,4bβ,10aβ)]-1,2,3,4a,4b,7,9,10,10a-decahydro-2,4b-dimethyl-7-oxo-2-phenanthrenecarboxylic acid methyl ester. The separation of this diastereomeric 14,15-secosteroid into (17R)- and (17S)-17-hydroxy-14,15-secoandrost-4-en-15-yn-3-one was accomplished by HPLC separation of the (S)-1-[(4-methylphenyl)sulphonyl]-2-pyrrolidinecarboxylate derivatives on a silica column. The crystal structure of (17S)-17-hydroxy-14,15-secoandrost-4-en-15-yn-3-one was then solved by X-ray diffraction analysis to establish unambiguously the absolute configuration of the diastereomeric 14,15-secosteroid.