Method of producing .alpha.-L-aspartyl-L-phenylalanine methylesters

A method of preparing .alpha.-L-aspartyl-L-phenylalanine alkylester in high yield without substantial isomer formation of the alkylester, which method comprises:

• (a) reacting L-aspartic acid with an alcohol, to provide an esterified aspartate compound with the beta-carboxyl group blocked by the ester group, and having a free alpha-carboxyl group;
• (b) reacting the amino group of the esterified aspartate compound with a carbobenzoxy halide, to provide an N-carbobenzoxyl, esterified, L-aspartate compound with a free alpha-carboxyl group;
• (c) reacting the N-carbobenzoxyl, esterified, aspartate compound in a coupling reaction with an alkylester of L-phenylalanine, by reaction of the free amino group of the L-phenylalanine with the free alpha-carboxyl group of the aspartate compound, to provide a coupled aspartate-phenylalanine compound;
• (d) hydrogenating the coupled compound, to reintroduce into the molecule the free amino group and one of the free carboxyl groups of the aspartate portion of the coupled compound;
• and
• (e) recovering the L-aspartyl-L-phenylalanine alkylester in a high yield, without substantial racemization of the .alpha.-L-aspartyl-L-phenylalanine alkylester.