200629-37-4Relevant academic research and scientific papers
Practical synthesis of an enantiomerically pure trans-4,5-disubstituted 2-pyrrolidinone via enzymatic resolution. Preparation of the LTB4 inhibitor BIRZ-227
Yee, Nathan K.,Nummy, Laurence J.,Byrne, Denis P.,Smith, Lana L.,Roth, Gregory P.
, p. 326 - 330 (1998)
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.
