PROTEASE-CATALYZED AND CHEMICAL PEPTIDE-BOND FORMATION WITH ALPHA-TRIFLUOROMETHYL SUBSTITUTED ALPHA-AMINO-ACIDS

Subtilisin, alpha-chymotrypsin and papain catalyzed hydrolyses of alph a-trifluoromethyl substituted N-benzyloxycarbonyl amino acid methylest ers (Z-TFM-Xaa-OMe) 1 can be achieved only in the case of 3,3,3-triflu oroalanine. Enzymatic incorporation of Z-TFM amino acids 2 into N-term inal position of dipeptides also fails. In contrary, dipeptides with a TFM amino acid moiety in N-terminal position, e. g. TFM-Phg-L-Phe-OMe 5, react with H-Leu-NH2 to give the corresponding tripeptides 6 in hi gh yield. Z protected dipeptide derivatives 8 with N-terminal TFM amin o acids can be obtained via 4-trifluoromethyl-5-(4H)-oxazolones 7.