Application of reversible amide-bond protection to suppress peptide segment epimerisation

Article abstract of DOI:10.1016/S0040-4039(97)10431-2

Reversible alkylation of the C-terminal amide-bond of a protected peptide segment with 2-hydroxy-4-methoxybenzyl dramatically suppresses epimerisation during activation and coupling. However, due to the formation of a 4,5-dihydro-8-methoxy-1,4-benzoxazepin-2(3H)-one species upon activation the rate of coupling is low. A safety-catch amide-bond protecting group, 6-hydroxy-5-methyl-1,3- benzoxathiolyl, has been designed to suppress epimerisation and couple with excellent yield.