Enantioselective Bioreduction of Medicinally Relevant Nitrogen-Heteroaromatic Ketones.

ABSTRACT

We herein report an enantioselective bioreduction of ketones that bear the most frequently used nitrogen-heteroaromatics 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 plant-mediated 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 route-scouting activities, and synthesis of other pharmaceutical molecules, favorably accelerating medicinal chemistry campaigns.