Develop an enzymatic carbenoid B–H insertion reaction for carborane functionalization. Carboranes are highly stable and structurally unique molecules used in diverse fields. Existing methods for functionalizing carboranes are limited, and we aim to use directed evolution to expand the substrate scope of enzymatic borylation to include various carboranes. These biocatalysts will be useful for developing regio- and stereospecific methods for carborane functionalization.
Further engineering of aziridine ring expansion enzymes. Presented with our findings that we can generate functionalized azetidines, ARL researchers proposed several promising functional handles that could be included on the azetidine core as energetic handles. Since our September meeting at ARL in 2019, the activity has been increased approximately one order of magnitude, resulting in ca. 36% yield of the desired product. Some further engineering is necessary to improve enzyme activity such that molecular cores can be provided to ARL in sufficient quantities for complete investigation of their potential for energetic applications.
Engineer cytochrome P411s for bicyclobutane synthesis. Our main objective is to expand the scope of P411-catalyzed carbene-transfer reactions by uncoupling the two carbene-transfer steps to permit the use of unique diazo substrates, ultimately furnishing bicyclobutanes with distinctive, functionalizable handles. We have placed special focus on the specific structures targeted by our collaborators at the ARL. Additionally, we are working on improving the scalability of this synthesis by incorporating both enzymatic steps in a single pot, abolishing the requisite purification of intermediates.
Engineer hemoproteins to catalyze carbenoid α-amino C–H insertion to generate molecules of interest to the ARL. Researchers at the ARL expressed an interest in carbenoid α-amino C–H insertion to stereoselectively incorporate fluoroalkyl groups into target substrates to construct high-energy molecules. We previously evolved enzymes to form iron-porphyrin carbenoids from trifluoromethylated diazo species, and we aim to engineer these enzymes to act on substrates of value to the ARL.