Studies on racemization associated with the use of benzotriazol-1-yl-tris (dimethylamino)phosphonium hexafluorophosphate (BOP)

The influence of the amount and nature of the necessary tertiary amine on racemization attending the BOP-mediated coupling of N-benzyloxycarbonylglycyl-dipeptides has been examined by determining the epimeric products by high-performance liquid chromatography. Racemization was encountered in all cases examined that included dichloromethane as solvent. The least racemization occurred when the base was diisopropylethylamine, the most when the base was N-methylmorpholine. Excess base promoted racemization. Racemization was significantly diminished but not eliminated when 1-hydroxybenzotriazole was added to the reaction mixtures. The above results pertain to the coupling of peptide segments; they do not pertain to the coupling of N-alkoxycarbonylamino acids.