Studies on the racemization of a stereolabile 5-aryl-thiazolidinedione.
The enantiomers of the stereolabile peroxisome proliferator-activated receptor (PPAR) agonist, 1, were isolated by preparative chiral chromatography and their absolute configuration established using a combination of chromatographic and NMR methods. Enantiomer interconversion was investigated under a variety of conditions, with rapid racemization being observed in most solvents, including all aqueous systems studied, irrespective of pH. Rapid racemization in both dog and human plasma was confirmed by chiral HPLC with MS detection.
Welch
Christopher J
CJ
Department of Process Research, Merck Research Laboratories, Merck & Co., PO Box 2000, Rahway, NJ 07065, USA. christopher_welch@merck.com
Kress
Michael H
MH
Beconi
Maria
M
Mathre
David J
DJ
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D006801:Humans; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D013237:Stereoisomerism; D013844:Thiazoles / Q000097:blood / Q000737:chemistry*; D045162:Thiazolidinediones
D013844:Thiazoles; D045162:Thiazolidinediones; C089946:2,4-thiazolidinedione