A versatile and selective chemo-enzymatic synthesis of β-protected aspartic and γ-protected glutamic acid derivatives

Two versatile, high yielding, and efficient chemo-enzymatic methods for the synthesis of β-protected Asp and γ-protected Glu derivatives using Alcalase are described. The first method is based on the α-selective enzymatic hydrolysis of symmetrical aspartyl and glutamyl diesters. The second method involving mixed diesters comprises a three-step protocol using (i) α-selective enzymatic methyl-esterification, (ii) chemical β-esterification, and finally (iii) α-selective enzymatic methyl ester hydrolysis. The yields of the purified β- and γ-esters range from 77% to 91%.