P450 Monooxygenases Enable Rapid Late-Stage Diversification of Natural Products C-H Bond Activation.

The biological potency of natural products has been exploited for decades. Their inherent structural complexity and natural diversity might hold the key to efficiently address the urgent need for the development of novel pharmaceuticals. At the same time, it is that very complexity, which impedes necessary chemical modifications such as structural diversification, to improve the effectiveness of the drug. For this purpose, Cytochrome P450 enzymes, which possess unique abilities to activate inert sp-hybridised C-H bonds in a late-stage fashion, offer an attractive synthetic tool. In this review the potential of cytochrome P450 enzymes in chemoenzymatic lead diversification is illustrated discussing studies reporting late-stage functionalisations of natural products and other high-value compounds. These enzymes were proven to extend the synthetic toolbox significantly by adding to the flexibility and efficacy of synthetic strategies of natural product chemists, and scientists of other related disciplines.