Efficient Enzymatic Synthesis of Carbamates in Water Using Promiscuous Esterases/Acyltransferases

Biocatalysis provides an attractive approach to facilitate synthetic reactions in aqueous media. Motivated by the discovery of promiscuous aminolysis activity of esterases, we exploited the esterase from Pyrobaculum calidifontis VA1 (PestE) for the synthesis of carbamates from different aliphatic, aromatic, and arylaliphatic amines and a set of carbonates such as dimethyl-, dibenzyl-, or diallyl carbonate. Thus, aniline and benzylamine derivatives, aliphatic and even secondary amines could be efficiently converted into the corresponding benzyloxycarbonyl (Cbz)- or allyloxycarbonyl (Alloc)-protected products in bulk water, with (isolated) yields of up to 99 %. Chemical synthesis performed under harsh reaction conditions often requires the need for protecting groups to prevent off-target reactions. While traditional chemical introduction of protecting groups disagrees with the principles of green chemistry, biocatalysis provides a promising alternative. Herein, we present an unprecedented enzymatic approach for the efficient synthesis of carbamate-protected amines in water achieving up to 99 % yield. image