Enantioselective Bioreduction of Medicinally Relevant Nitrogen-Heteroaromatic Ketones

We herein report an enantioselective bioreduction of ketones that bear the most frequently used nitrogenheteroaromatics in FDA-approved drugs. Ten varieties of these nitrogen-containing heterocycles were systematically investigated. Eight categories were studied for the first time and seven types were tolerated, significantly expanding the substrate scope of plantmediated reduction. By use of purple carrots in buffered aqueous media with a simplified reaction setup, this biocatalytic transformation was achieved within 48 h at ambient temperature, offering medicinal chemists a pragmatic and scalable tool to access a broad variety of nitrogen-heteroaryl-containing chiral alcohols. With multiple reactive sites, the structurally diverse set of chiral alcohols can be used for library compound preparation, early routescouting activities, and synthesis of other pharmaceutical molecules, favorably accelerating medicinal chemistry campaigns.