Abstract:

Deuterated compounds display unique properties, and thus have important applications in chemistry, biology, and related areas. For example, deuterated compounds are widely used in elucidating reaction mechanism in organic synthesis because deuterium atom has similar chemical reactivities to hydrogen atom but different magnetic property and mass. In pharmaceutical industry, deuterium-labeled compounds are used for improving the metabolism and pharmacokinetic properties of newly developed pharmaceuticals due to the higher chemical inertness of C—D bonds compared with the C—H bonds. The first deuterated drug, Austedo^TM, was approved in 2017 by the US Food and Drug Administration, which has greatly stimulated the research of deuterium incorporation in pharmaceuticals.Traditional chemical methods for introducing deuterium into compounds rely heavily on transition metal catalysis performed under harsh reaction conditions using complicated ligands with low selectivity, which limit their broad applications. Thus, developing an effective, highly selective, low-cost, and environmental-friendly process for deuteration is highly desirable. Comparing with chemical catalysts, enzymes offer a powerful route for producing chemicals due to their green nature and high selectivity. Thus, biocatalysis has been regarded as an attractive strategy for deuteration. So far, to the best of our knowledge, reported biocatalytic deuteration methods mainly include three types: hydrogen deuterium exchange (HDE), reduction deuteration and decarboxylation deuteration. The biocatalytic production of HDE is the most efficient synthesis process with good atom-economy, which mostly effectively introduces the isotope into the α-position of the carboxyl group. Bioreductive deuteration usually uses a NADH-dependent reductase with D₂O to construct deuterated chiral alcohols or amines. The decarboxylation deuteration offers good selectivity to introduce deuterium into the carboxyl group using carboxylic acids as low-cost starting materials. In this review, we describe recent advances in the three types of biocatalytic deuteration processes respectively. In these cases, D₂O is used as the main source for deuterium atoms. Although studies on the preparation of deuterated compounds by biocatalysis are still in the initial stage, it is expected to be flourish rapidly due to the importance of deuterated compounds.