Tandem deprotection/coupling for peptide synthesis in water at room temperature

Abstract

A tandem deprotection/coupling sequence is reported for solution-phase peptide synthesis in water under micellar catalysis conditions using the designer surfactant TPGS-750-M. Cbz deprotection followed by peptide coupling in the presence of COMU and 2,6-lutidine afforded polypeptides containing up to 10 amino acid residues. A broad scope characterizes this new technology. No epimerization has been detected. The associated E Factors, as a measure of “greenness” and known to be extremely high for peptide couplings, have been reduced to less than 10 due to the step-economy and minimal amounts of organic solvent needed for product extraction.