Rapid microwave-assisted solution-phase peptide synthesis

Rapid microwave-assisted solution-phase peptide synthesis protocol has been developed. The reaction temperature of 50 °C, 40 W and short coupling time of 28 min gave racemization-free synthesis of peptides in 50-80% yield. The method is applicable with equal ease in coupling both side-chain protected and unprotected amino acids indicating reactive-functional group tolerance and high atom-economy. In the case of dipeptides, DIC/HONB-mediated coupling rendered the best results. In the case of tri- and tetrapeptides, HATU/HOAt/DIEA emerged as the best coupling combination.