title: Structure determination of chiral sulfoxide in diastereomeric bicalutamide derivatives.
abstract: 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.
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
authors: Wei
authors: W
authors: Li
authors: Dong Jin
authors: DJ
authors: Hwang
authors: Dieter
authors: D
authors: Cremer
authors: Hyun
authors: H
authors: Joo
authors: Elfi
authors: E
authors: Kraka
authors: Juhyun
authors: J
authors: Kim
authors: Charles R
authors: CR
authors: Ross
authors: Viet Q
authors: VQ
authors: Nguyen
authors: James T
authors: JT
authors: Dalton
authors: Duane D
authors: DD
authors: Miller
mesh_terms: D059002:Androgen Receptor Antagonists; D000813:Anilides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D009570:Nitriles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011789:Quantum Theory; D011944:Receptors, Androgen / Q000378:metabolism; D012451:Safrole / Q000031:analogs & derivatives* / Q000737:chemistry; D013237:Stereoisomerism; D014105:Tosyl Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D059002:Androgen Receptor Antagonists; D000813:Anilides; D009570:Nitriles; D011944:Receptors, Androgen; D014105:Tosyl Compounds; C053541:bicalutamide; D012451:Safrole; C005746:sulfoxide