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Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
Studies on the racemization of a stereolabile 5-aryl-thiazolidinedione
Christopher J Welch1, Michael H Kress, Maria Beconi
1Department of Process Research, Merck Research Laboratories, Merck & Co., PO Box 2000, Rahway, NJ 07065, USA. christopher_welch@merck.com
Abstract:
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.
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