ENZYMATIC PROCESS FOR PRODUCING DIPEPTIDES

摘要

Dipeptides having the general formula H-A-B-Y wherein A represents an optionally side-chain protected L- or D- alpha -amino acid or omega -amino acid and B represents an optionally side-chain protected L- or D- alpha -aminocarboxylic acid which may be the same as or different from A, an L- or D-aminophosphonic acid or L- or D-aminosulfonic acid or the corresponding omega -amino acids or salts and hydrates thereof, and Y is OH or a C-terminal blocking group, are prepared by reacting a substrate component, which is an amino acid derivative having the formula wherein A is as defined above, R<1> represents hydrogen, alkyl, aryl or aralkyl optionally substituted with inert substituents or an alpha -des-amino fragment of an amino acid, and R<2> and R<3> are the same or different and each represents hydrogen, alkyl, aryl or aralkyl optionally substituted with inert substituents, with a nucleophile component which when A = B may be formed in situ and is selected from (a) L-amino acids having the formula H-B-OH (b) L-amino acid amides having the formula wherein B is an L-amino acid, and R<2> and R<3> have the above meaning, except that when R<2> represents hydrogen, R<3> may also represent hydroxy or amino (c) L-amino acid esters having the formula H-B-OR<4> wherein B is an L-amino acid, and R<4> represents alkyl, aryl or aralkyl, and (d) optionally acid group protected straight chain or branched amino phosphonic acids or amino sulfonic acids having the formula NH2CxHzPO3H2 or NH2CxHzSO3H wherein x is 1-6 and z is 2-12 in the presence of a serine or thiol carboxypeptidase from yeast or of animal, vegetable or other microbial origin, preferably CPD-Y from yeast in an aqueous solution or suspension having a pH value between 5 and 10.5 optionally containing an organic solvent and/or a salt, and then, if desired, cleaving a present side-chain protecting group or protective group Y and/or, if desired, converting the resulting dipeptide derivative to a salt or hydrate. The process allows for production of L,L-, LD-, DL- and DD-dipeptides without risk of racemization in a simple and economic manner.