Enzymatic coupling reaction of N-protected-L-aspartic acid and phenylalanine methyl ester
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United States of America Patent
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Dec 2, 1997
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app pub date -
Oct 11, 1996
filing date -
Oct 11, 1995
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Abstract
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.
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