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Design and Diastereoselective Synthesis of C‐2,C‐20‐Diaryl Steroidal Derivatives
Author(s) -
Rey Jullien,
O'Riordan Timothy J. C.,
Hu Haipeng,
Snyder James P.,
White Andrew J. P.,
Barrett Anthony G. M.
Publication year - 2012
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201200190
Subject(s) - chemistry , diastereomer , trifluoromethanesulfonate , ketone , steroid , enol , carbonylation , nucleophile , stereochemistry , epimer , aryl , enol ether , ether , chiral auxiliary , enantioselective synthesis , pregnenolone , combinatorial chemistry , organic chemistry , catalysis , biochemistry , alkyl , carbon monoxide , hormone
A novel and efficient synthetic strategy to access unique C‐2 substituted steroid analogues 3 and 4 is described. The unusual C‐2 aryl ether analogues 3 were shown to act as virtual antagonists of LRH‐1 and were prepared as single diastereoisomers, employing a fifteen‐step sequence from pregnenolone ( 9 ). The key steps include the stereoconvergent nucleophilic displacement of an epimeric mixture of 3‐keto 2‐bromo steroids, chemoselective carbonylation of an enol triflate and conversion of a thiopyridyl ester into an aryl ketone. The related C‐2 benzyl analogues 4 were prepared in a similar manner.