Determination of the absolute configuration and solution conformation of a novel disubstituted pyrrolidine acid A by vibrational circular dichroism.
Compound A, a novel disubstituted pyrrolidine acid, is a member of a new class of agents that are potentially useful for the treatment of diabetes and dyslipidemia. The absolute configuration of this compound was determined by using vibrational circular dichroism (VCD). The results are in agreement with the assignments based on both X-ray analysis and the stereo-selective chemical synthesis. During VCD analysis, the solution conformation for a portion of compound A in CDCl(3) was also established. The compound is found to associate as an H-bonded carboxylic acid "dimer" in CDCl(3) solution, and VCD calculations on a model dimer fragment were required to establish the absolute configuration.
Freedman
Teresa B
TB
Department of Chemistry, Syracuse University, Syracuse, New York 13244, USA. jack.gougoutas@bms.com
Cao
Xiaolin
X
Phillips
Linda M
LM
Cheng
Peter T W
PT
Dalterio
Richard
R
Shu
Yue-Zhong
YZ
Zhang
Hao
H
Zhao
Ning
N
Shukla
Rajesh B
RB
Tymiak
Adrienne
A
Gozo
Stephen K
SK
Nafie
Laurence A
LA
Gougoutas
Jack Z
JZ
D000143:Acids / Q000032:analysis* / Q000737:chemistry*; D002942:Circular Dichroism / Q000379:methods*; D019281:Dimerization; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011759:Pyrrolidines / Q000032:analysis* / Q000737:chemistry*; D012996:Solutions / Q000737:chemistry; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism
D000143:Acids; D011759:Pyrrolidines; D012996:Solutions; C032519:pyrrolidine