Mechanistic Studies on Racemization of Chiral 2-Arylthiazolidinons
Tatsuya Kato, Tomokazu Ozaki · Heterocycles · 2001
Mechanistic studies on racemization of chiral 3-[(2S)-2-(3,5-di-tertbutyl-4-hydroxyphenyl)-4-oxo-1,3-thiazolidin-3-yl]propanoic acid is described.This racemization is triggered by deprotonation of phenolic hydroxyl group.We propose that the racemization proceeds via a novel mechanism involving ring opening-closure equilibrium of the thiazolidinone ring.In the course of our recent studies on a novel cardioprotective drug, we found (S)-thiazolidin-4-one (CP-060S) possessed not only potent Ca 2+ antagonistic activity but Ca 2+ overload inhibition and antioxidant activities as well. 1,2 e previously reported a practical synthetic method for this compound 3 in which racemic carboxylic acid intermediate (1) was optically resolved by selective crystallization from a mixture of diastereomeric salts with chiral amine (2).Furthermore, recycling via racemization of the mixture rich in undesired (R)-1, obtained from the mother liquid in the resolving process, resulted in remarkable improvement of the conversion yield as shown in Scheme 1. Scheme 1. Synthetic Route of CP-060S via Optical Resolution and Racemization CycleHO N S O CO 2 H Ph N Ph H Me (R)-1 aq NaOH optical resolution 2