PRACTICAL SYNTHESIS OF AN ENANTIOMERICALLY PURE TRANS-4,5-DISUBSTITUTED 2-PYRROLIDINONE VIA ENZYMATIC RESOLUTION - PREPARATION OF THE LTB4 INHIBITOR BIRZ-227

Citation
Nk. Yee et al., PRACTICAL SYNTHESIS OF AN ENANTIOMERICALLY PURE TRANS-4,5-DISUBSTITUTED 2-PYRROLIDINONE VIA ENZYMATIC RESOLUTION - PREPARATION OF THE LTB4 INHIBITOR BIRZ-227, Journal of organic chemistry, 63(2), 1998, pp. 326-330
Citations number
18
Categorie Soggetti
Chemistry Inorganic & Nuclear
ISSN journal
00223263
Volume
63
Issue
2
Year of publication
1998
Pages
326 - 330
Database
ISI
SICI code
0022-3263(1998)63:2<326:PSOAEP>2.0.ZU;2-7
Abstract
A practical synthesis of the enantiomerically pure BIRZ-227 (1), a,LTB 4 inhibitor, has been developed. The key steps include the effective s ynthesis of the trans-diarylpyrrolidinone (+/-)-8 and the enzymatic re solution of N-acetoxymethyl pyrrolidinone (+/-)-10 by immobilized Lipa se Novozym 435. Reduction of pyrrolidinone (+)-8 with borane and subse quent coupling with chlorobenzoxazole 2 furnished BIRZ-227 in high ena ntiomeric purity (99% ee). The overall process described herein requir ed no chromatographic separation and is amenable to the preparation of multikilogram quantities of the desired drug candidate in a cost-effe ctive manner.