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 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.
Hu
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Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Sherwin
P F
PF
Covey
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DF
D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); D003460:Crystallization; D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D012632:Secosteroids / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D013237:Stereoisomerism
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)