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Structure determination of chiral sulfoxide in diastereomeric bicalutamide derivatives
Author(s) -
Li Wei,
Hwang Dong Jin,
Cremer Dieter,
Joo Hyun,
Kraka Elfi,
Kim Juhyun,
Ross Charles R.,
Nguyen Viet Q.,
Dalton James T.,
Miller Duane D.
Publication year - 2009
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.20642
Subject(s) - chemistry , diastereomer , stereocenter , sulfoxide , asymmetric carbon , absolute configuration , chirality (physics) , proton nmr , stereochemistry , dimethyl sulfoxide , crystallography , organic chemistry , enantioselective synthesis , catalysis , optically active , nambu–jona lasinio model , chiral symmetry breaking , physics , quantum mechanics , quark
We report on the synthesis and investigation of two diastereomers ( 5a and 5b ) of a new bicalutamide analog with an asymmetric carbon atom and a chiral sulfoxide group. These bicalutamide analogs are novel androgen receptor antagonists with biological activities that depend significantly on the configuration of their stereogenic centers. We determined the absolute configuration at the SO center by combining X‐ray and NMR measurements with quantum chemical calculations. Since 5a and 5b failed to yield satisfactory crystals for X‐ray crystal structure determination, analogs 6a and 6b differing in only one remote functional group relative to the chiral sulfoxide were synthesized, which yielded satisfactory crystals. X‐ray structure determination of 6a and 6b provided the absolute configuration at the chiral sulfoxide. Since the structural difference between 5 and 6 is remote from the chiral sulfoxide, the structural assignment was extended from the diastereomers of 6 to those of 5 provisionally. These assignments were verified with the help of measured and DFT‐calculated proton and carbon NMR chemical shifts. Chirality, 2008. © 2009 Wiley‐Liss, Inc.