Activation of diketopiperazine formation by alkylammonium carboxylate salts and aprotic dipolar protophobic solvents.

ABSTRACT

Diketopiperazine formation from the N-terminal residues of a peptide chain is accelerated by aprotic dipolar protophobic solvents and catalyzed in organic solvents by alkylammonium carboxylate salts. The t1/2 for the first-order reaction of H-Ala-Pro-NH2 x TFA falls from 20 d in methanol to 3.6 min in acetonitrile containing 0.02 mol dm(-3) triethylammonium acetate; for H-Ala-Ala-NH2 x TFA in the same reaction media t1/2 falls from an unmeasurably long time to 1.3 d.