A PROCESS FOR ENZYMATIC PRODUCTION PRODUCTION OF DIPEPTIDES

摘要

Dipeptides having the general formula H-A-B-Y, wherein A represents an optionally side-chain protected L- or D-α-amino acid or φ-amino acid and B represents an optionally side-chain protected L- or D-α-amino-carboxylic acid which may be the same as or different from A, and L- or D-aminophosphonic acid or L- or D-aminosulfonic acid or the corresponding φ-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 formula (I), wherein A is as defined above, R1 represents hydrogen, alkyl, aryl or aralkyl optionally substituted with inert substituents or an α-des-amino fragment of an amino acid, and R?2 and R3¿ 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 formula (II), wherein B is an L-amino acid, and R?2 and R3¿ have the above meaning, except that when R2 represents hydrogen, R3 may also represent hydroxy or amino, (c) L-amino acid esters having the formula H-B-OR4, wherein B is an L-amino acid, and R4 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 NH¿2?CxHzPO3H2 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.