Enantioselective Carbon Isotope Exchange
Michael G. J. Doyle, Odey Bsharat, Anna Sib, Volker Derdau, Rylan J. Lundgren
Abstract
The synthesis of isotopically labeled organic molecules is vital for drug and agrochemical discovery and development. Carbon isotope exchange is emerging as a leading method to generate carbon-labeled targets, which are sought over hydrogen-based labels due to their enhanced stability in biological systems. While many bioactive small molecules bear carbon-containing stereocenters, direct enantioselective carbon isotope exchange reactions have not been established. We describe the first example of an enantioselective carbon isotope exchange reaction, where (radio)labeled α-amino acids can be generated from their unlabeled precursors using a stoichiometric chiral aldehyde receptor with isotopically labeled CO 2 followed by imine hydrolysis. Many proteinogenic and non-natural derivatives undergo enantioselective labeling, including the late-stage radiolabeling of complex drug targets.