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