Current Organic Chemistry - Volume 4, Issue 3, 2000

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 hydro-carbons, 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.

Even though the use of enzymes as catalyst in synthetic organic chemistry is widespread, their application in C-C- bond-forming reactions is still poor. There are several types of enzymes that catalyze C-C bond formation and the most used are the most readily available. Currently, the availability of these enzymes is increasing. This review will cover synthetic applications of three types of enzymes related to three different reactions aldol reaction, acyloin condensation, and cyanohydrin reaction. The enzymes involved, aldolases, pyruvate decarboxylase and oxynitrilases, are all readily available.

This review covers recent progress in the use of chiral Lewis acid catalysts in ene-reactions which involve carbonyl and imine compounds as enophiles. Chiral Lewis acid catalysts containing aluminum, titanium, ytterbium and copper are critically reviewed. Synthetic applications of recent systems are specifically discussed.

This review covers recent developments in the area of morphine synthesis and biosynthesis. Literature is reviewed since the publication of the last major review. The first part of the chapter discusses recent advancements in biosynthesis of morphine alkaloids. Total syntheses published since 1996 are reviewed next and the third section discusses all published approaches to morphine skeleton. At the end of the of the chapter, an additional reference list is provided for synthesis of medicinally important derivatives, improvements in alkoloid interconversion, as well as a list of all dissertations dealing with morphine synthesis.