Practical Synthesis of an Enantiomerically Pure trans-4,5-Disubstituted 2-Pyrrolidinone via Enzymatic Resolution. Preparation of the LTB4 Inhibitor BIRZ-227
The Journal of Organic Chemistry1998Vol. 63(2), pp. 326–330
Citations Over Time
Abstract
A practical synthesis of the enantiomerically pure BIRZ-227 (1), a LTB4 inhibitor, has been developed. The key steps include the effective synthesis of the trans-diarylpyrrolidinone (±)-8 and the enzymatic resolution of N-acetoxymethyl pyrrolidinone (±)-10 by immobilized Lipase Novozym 435. Reduction of pyrrolidinone (+)-8 with borane and subsequent coupling with chlorobenzoxazole 2 furnished BIRZ-227 in high enantiomeric purity (99% ee). The overall process described herein required no chromatographic separation and is amenable to the preparation of multikilogram quantities of the desired drug candidate in a cost-effective manner.
Related Papers
- → Enantiomeric enrichment of non-racemic mixtures of binaphthol with non-chiral packings(1996)47 cited
- → Enantiomeric enrichment by the use of density differences between racemic compounds and optically active enantiomers(1995)16 cited
- → Enantioselective reduction of ketones by borane catalysed by oxazaphospholidine oxides(1996)44 cited
- → Colour indicator for enantiomeric excess and assignment of the configuration of the major enantiomer of an amino acid ester(2002)26 cited
- → Chiral polyethers derived from BINOL and ECH as highly enantioselective and efficient catalysts for the borane reduction of prochiral ketones(2015)8 cited