TY - JOUR
T1 - 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
AU - Hu, Yuefei
AU - Sherwin, Paul F.
AU - Covey, Douglas F.
N1 - Funding Information:
This work was supported by NIH Research Grant HD 19746. Assistance was also provided by the Washington University High-Resolution NMR Service Facility (supported in part through NIH Biomedical Research Support Shared Instrument Grant 1 S 10 RR02004 and a gift from the Monsanto Company) and by the Washington University Mass Spectrometry Service Facility (supported by NIH RR00954).
PY - 1995/3
Y1 - 1995/3
N2 - (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.
AB - (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.
KW - 14,15-secosteroids
KW - X-ray structure analysis
KW - chiral resolution
KW - hydroxysteroid dehydrogenase inhibitors
UR - http://www.scopus.com/inward/record.url?scp=0028948088&partnerID=8YFLogxK
U2 - 10.1016/0039-128X(94)00044-D
DO - 10.1016/0039-128X(94)00044-D
M3 - Article
C2 - 7792826
AN - SCOPUS:0028948088
SN - 0039-128X
VL - 60
SP - 250
EP - 255
JO - Steroids
JF - Steroids
IS - 3
ER -