1.1.5.3.2.3.1. Development of Remote Oxidation in Chemistry
The oxidation by cytochrome P-450 inspired chemists to develop processes called remote oxidation, in which the reagents and templates are attached to substrates that could reach far from their attachment point (from ring A of the steroid all the way to ring D at the other end) and perform selective reactions on particular spots because of the geometry imposed by the attached reagent or template. In the enzyme mimic, Breslow and his group have synthesized a metalloporphyrin carrying cyclodextrin groups that would reversibly bind substrates such as steroids. These mimics of cytochrome P-450 performed selective oxidations that are of practical interest, with thousands of turnovers. The result was selective oxidation of particular C–H bonds that was possible only with natural biological enzymes.

Characteristic features and results of reactions done by the enzyme P450 mimic:

1. Metalloporphyrins with attached cyclodextrin groups can bind various steroid derivatives and catalyze their selective hydroxylations.
2. The selectivity observed are consistent with molecular and computer models of the complexes.
3. In the best cases, hundreds and even thousands of catalytic turnovers of the selective reactions can be achieved.
4. The geometries of the complexes override intrinsic reactivities preventing oxidation of an otherwise reactive secondary carbinol or of a carbon-carbon double bond. This mimics selectivity effects typically seen only in enzymatic reactions.
5. The catalytic selective hydroxylation at carbon 9 in an androstane derivative provides entry into potential corticosteroid precursors.

Figure 1.7: An artificial cytochrome P450 that hydroxylates inactivated carbons with regio- and stereoselectivity and useful catalytic turnovers.

Figure 1.8: Hydroxylation of inactivated carbons with regio- and stereoselectivity and useful catalytic turnovers by an artificial cytochrome P450.