초록 ▼

The invention relates to a process for the preparation of N-protected-L-aspartyl-L-phenylalanine methyl ester by enzymatic coupling of an N-protected-L-aspartic acid and L- or DL-phenylalanine methyl ester in an aqueous solution with formation of a precipitate using a thermolysin-like protease enzym

The invention relates to a process for the preparation of N-protected-L-aspartyl-L-phenylalanine methyl ester by enzymatic coupling of an N-protected-L-aspartic acid and L- or DL-phenylalanine methyl ester in an aqueous solution with formation of a precipitate using a thermolysin-like protease enzyme, wherein a water-immiscible organic solvent is added to and blended with the reaction system during the formation of the precipitate in the course of the coupling reaction, which organic solvent has a relatively high affinity for the precipitate. The process is particularly suitable as a continuous process. The method results in lower enzyme deactivation during and after the enzymatic coupling reaction and in larger and thicker precipitated crystals.

대표청구항 ▼

A process for preparing N-protected-L-aspartyl-L-phenylalanine methyl ester by enzymatic coupling of an N-protected-L-aspartic acid with L- or DL-phenylalanine methyl ester in an aqueous solution and wherein a precipitate is formed by use of a thermolysin-like protease enzyme, which process comprise

A process for preparing N-protected-L-aspartyl-L-phenylalanine methyl ester by enzymatic coupling of an N-protected-L-aspartic acid with L- or DL-phenylalanine methyl ester in an aqueous solution and wherein a precipitate is formed by use of a thermolysin-like protease enzyme, which process comprises, during the course of formation of the said precipitate, adding and blending into said aqueous solution an organic solvent having a relatively high affinity for said precipitate and which, under the reaction conditions employed, is water-immiscible and forms a second liquid phase.