Process for the enzymatic production of dipeptides.

摘要

Dipeptides or related compounds of the formula H-A-B-Y,wherein A is an L- or D- alpha -amino acid residue or omega -amino acid residue, B is an L- or D- alpha -aminocarboxylic acid residue, an L- or D-aminophosphonic acid residue or L- or D-aminosulfonic acid residue or the corresponding omega -amino acids or salts and hydrates thereof, and Y is OH, H, alkyl, aryl, aralkyl or a C-terminal blocking group, -or BY is an amino alcohol residue B<1>-CHY<1>-OH, wherein B<1> is a decarboxy derivative of the aminocarboxylic acid as defined with relation to B, and Y<1> is H, alkyl, aryl or aralkyl are produced by reacting a substrate component wherein A is as defined above, R<1> is alkyl, aryl or aralkyl or an alpha -des-amino fragment of an amino acid, R<2> and R<3> are hydrogen, alkyl, aryl or aralkyl with a nucleophile component selected from amino acids or their amides, esters, aldehydes or ketones of the formula wherein B is an aminocarboxylic acid residue as defined above, R<2> and R<3> have the above meaning, or when R<2> is hydrogen, R<3> is also hydroxy or amino, R<4> and R<8> are alkyl, aryl or aralkyl, and may also be H, aminophosphonic acids or aminosulfonic acids NH2CxHzPO3R<5>R<6> or NH2CxHzSO3R<7> wherein R<5>, R<6> and R<7> are hydrogen, alkyl, aryl or aralkyl, x is 1-6 and z is 2-12, and amino alcohols H-B<1>-CHY<1>-OH wherein B<1> and Y<1> are as above in the presence of an amidase or esterase enzyme different from serine or thiol carboxypeptidases, preferably a serine or thiolendoprotease, lipase, esterase or glycosidase in solution or dispersion, 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 LL-, LD-, DL- and DD-dipeptides without risk of racemization in a simple and economic manner.