C-C bond cleavage reactions catalyzed by cytochrome P450 enzymes

AbstractCytochrome P450 (P450, CYP) enzymes are the major catalysts involved in drug metabolism, as well as general oxidations of vitamins, steroids, natural products, and industrial chemicals. The general catalytic mechanism involves a high valent FeO Complex termed Compound I (formally FeO3+) which can be used to explain most hydroxylations, dealkylations, epoxidations, and many other reactions. P450s also catalyze C-C bond formations and cleavages. Some of the latter are often seen with drugs and natural products, as well as with steroids. The steroid cleavage reactions have been studied in detail for many years, using a variety of approaches. In some cases, there is strong evidence that Compound I mechanisms, using an electrophilic FeO3+ entity, are involved. In a few cases, alternatives —mainly Compound 0 (Fe3+-O2¯)—have been proposed. The evidence is reviewed for several important human P450 enzymes.

Source: Medicinal Chemistry Research - May 27, 2023 Category: Chemistry Source Type: research