Studies on racemization during couplings using a series of model tripeptides involving activated residues with...

Racemization studies have been carried out using as model tests couplings of N-benzyloxycarbonylglycyl-L-X with benzyl NE-benzyloxycarbonyl-L-lysinate followed by deprotection and analysis for the diastereomeric tripeptides with an amino acid analyzer, for X = alanine, leucine, phenylalanine, valine and isoleucine. The order of susceptibility to racemization of residues during these segment couplings depends on whether the solvent is polar or apolar, with isoleucyl and valyl, followed by phenylalanyl, being the most susceptible ones in polar solvents. The racemization depressing effect of some additives on carbodiimide-mediated couplings has been examined. Reconciliation of apparent discrepancies in data in the literature on the relative merits of l-hydroxy-benzotriazole and N-hydroxysuccinimide is made on the basis of the nature of the model tests used in acquiring the data.