Browsing by Author "Ilie, Adriana"

The achiral cyclohexene derivative dimethyl cis-1,2,3,6-tetrahydrophthalate has been subjected to oxidation catalyzed by cytochrome P450 monooxygenase P450-BM3, leading to diastereoselective epoxidation rather than oxidative hydroxylation. This reaction occurs with 94% diastereoselectivity in favor of the anti-epoxide, in contrast to m-CPBA which delivers unselectively a 70:30 mixture of anti/syn diastereomers. The experimental results are nicely explained on a molecular level by docking experiments and molecular dynamics computations.

Wild-type P450-BM3 is able to catalyze in a highly regio- and diastereoselective manner the oxidative hydroxylation of non-activated disubstituted cyclohexane derivatives lacking any functional groups, including cis- and trans-1,2-dimethylcyclohexane, cis- and trans-1,4-dimethylcyclohexane, and trans-1,4-methylisopropylcyclohexane. In all cases except chiral trans-1,2-dimethylcyclohexane as substrate, the single hydroxylation event at a methylene group induces desymmetrization with simultaneous creation of three centers of chirality. Certain mutants increase selectivity, setting the stage for future directed evolution work.