Biocatalytic route scouting and enzyme screening toward the synthesis of α-benzyl L-glutamate

We here report four biocatalytic approaches for the synthesis of the protected amino acid building block α-benzyl L-glutamate. Screenings of these routes to identify active and selective enzymes were conducted, and major hits were confirmed in retest reactions. In the first approach, N-Boc L-glutamic acid is mono-benzylesterified by the protease Alcalase with 81% yield; and in the other three approaches, a biocatalytic γ-selective hydrolysis of α,γ-dibenzyl L-glutamate, a selective amide hydrolysis of α-benzyl L-glutamine, and a selective lactam hydrolysis of alpha-benzyl L-pyroglutamate is performed with up to 71% yield.