The Desaturative Role of Cytochrome P450 Inorganic Analogues

Abstract

While there is a wide range of active species and biomolecules in the pharmaceutical world, all of these agents are built from the same fundamental chemical building blocks. Olefins, formed from desaturated hydrocarbons, are a primary constituent of this foundation. The efficient production of these building blocks, however, remains elusive. Therefore, the direct conversion of unactivated aliphatic C-H bonds to their unsaturated counterparts could change the landscape of organic synthesis. Desaturation is uniquely difficult to accomplish as the catalyst must be sufficiently reactive to perform two hydrogen atom abstractions. However, a highly reactive catalyst will yield overoxidized products. Understanding the oxidative reactions of Cytochrome P450 enzymes and their biomimetic analogues can provide insights into this powerful biosynthetic transformation. Additionally, investigating the effect of the steric and electronic environment of the metalloprotein on reaction outcome will allow synthetic chemists to divert the paradigmatic oxygen rebound step for epoxide product formation. Specifically, fine-tuning of the axial and equatorial ligands is necessary to create a catalyst capable of breaking two C-H bonds while preventing overoxidation of the substrate. The insights gained from this review and analysis of the properties of CYP enzyme analogues will hopefully allow the synthetic community to answer the question of how metalloporphyrins can act as a desaturase in lieu of their typical role as a hydroxylase.