Theoretical study of enantioenriched aminohydroxylation of styrene catalyzed by an engineered hemoprotein

Abstract

AbstractTransforming olefins to chiral amino alcohols is a useful approach to synthesize biologically active natural products and numerous drugs. A recent study has demonstrated a promising and synthetic value of an engineered hemoprotein for catalyzing olefins to chiral amino alcohols with 2500 total turnover numbers and 90% ee. Density functional theory (DFT) calculation has been used to systematically investigate the detailed mechanisms of the aforementioned process. One electron transfers from Fe atom to HN–nitrene in the iron–nitrene intermediate formation. Subsequently, styrene aziridination, singlet state is characterized by a nonradical, concerted nonsynchronous mechanism, while a radical and stepwise mechanism for triplet. Through hydrolysis reaction forming amino alcohol enantiomers, radical intermediate in triplet state without ring‐opening process is obviously more feasible than singlet aziridine, where the energy barrier difference between triplet and singlet approaches to 20.00 kcal/mol. Moreover, due to the hydrogen bond effect, the water dimer‐assisted hydrolysis reaction is effective to reduce the energy barrier by about 7.00 kcal/mol compared with one water assisted in triplet; however, the energy barrier difference in singlet is unapparent with only 0.18 kcal/mol accompanied with ring‐opening process. Further, homology modeling shows that the reactivity and enantioselectivity can be attributed to the structure of the enzyme active pocket. This study sheds light on the mechanism of engineered hemoprotein‐mediated amino alcohols synthesis and shows the development of biological catalysts.