Studies on the racemization of a stereolabile 5‐aryl‐thiazolidinedione

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.

Serendipitous discovery of a pH-dependant atropisomer bond rotation: Toward a write-protectable chiral molecular switch?☆

“…Column screening was carried out using a standard gradient approach described previously. [15] The optimized isocratic analytical chiral SFC method employed a Chiralpak AD-H column (250 × 4.6 mm), with an eluent of 20% methanol in carbon dioxide at 1.5 mL/min, 200 bar pressure, 35 • C oven temperature, 215 nm.…”

Use of Enantioselective Synthesis and Preparative Chiral Chromatography to Access a Challenging Enantiopure Pharmaceutical Candidate from a Mixture of Four Stereoisomers

“…In this study, more than a dozen compounds representing several distinct synthetic routes to 1 were examined by chiral SFC using a previously described standard method development screening approach [9].…”

Determination of MK-0767 enantiomers in human plasma by normal phase LC–MS/MS

“…Suzuki et al reported a HPLC/UV method to separate troglitazone stereoisomers, a TZD based compound with two chiral centers, in manufacturing process and stability testing [7]. Welch et al also reported using Whelk-O column to separate a stereolabile 5-aryl-thiazolidinedione [8]. The present paper describes an analytical method which employs single step liquid-liquid extraction for the sample preparation, normal phase HPLC for enantiomer separation, and MS/MS for detection of the analytes.…”