Cytochrome P450s: Potential Catalysts for Asymmetric Olefin Epoxidations

Carlos   A.   Martinez; Jon   D.   Stewart

Abstract

Cytochrome P450 monooxygenases (P450s; EC 1.14.14.1) catalyze a variety of oxidations, although they are best known for hydroxylations and olefin epoxidations. Such enzymes also might be useful in asymmetric synthesis since different forms accept aromatic polycyclic hydrocarbons, prochiral and chiral olefins with a variety of aromatic and aliphatic substituents. This review summarizes all of the synthetically-relevant epoxidation reactions catalyzed by mammalian and selected bacterial members of the P450 superfamily published before August 1999. Mammalian liver tissue contains a variety of cytochrome P450s and in some cases their levels can be influenced by prior drug treatment. Crude preparations (microsomes) derived from these tissues also can be used to catalyze epoxidations, and these results are compared with those obtained using purified mammalian cytochrome P450 isoforms such as CYP2B4, CYP2E1, CYP2A6 and CYP2C8. Several individual bacterial representatives such as P450cam, P450BM3 and P450terp, whose X-ray crystal structures have been determined, are also considered. A number of recent developments are also discussed including the elucidation of substrate recognition sites, the use of P450s expressed in microbial hosts, immobilized enzyme systems and directed evolution of individual P450s to provide variants with properties better suited to synthetic applications.