title: 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.
abstract: (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 3 alpha-hydroxysteroid dehydrogenase. This manuscript describes the synthesis of this diastereomeric 14,15-secosteroid from [2S-(2 alpha,4a alpha,4b beta, 10a beta)]- 1,2,3,4a,4b,7,9,10,10a-decahydro-2,4b-dimethyl-7-oxo-2-phenanth renecarboxylic 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.
authors.affiliation: Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Hu
authors.forename: P F
authors.initials: PF
authors.lastname: Sherwin
authors.forename: D F
authors.initials: DF
authors.lastname: Covey
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003460:Crystallization; D018360:Crystallography, X-Ray; D008099:Liver / Q000201:enzymology; D008958:Models, Molecular; D015394:Molecular Structure; D051381:Rats; D012632:Secosteroids / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: C094247:17-hydroxy-14,15-secoandrost-4-en-15-yn-3-one; D012632:Secosteroids; D015096:3-Hydroxysteroid Dehydrogenases; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)