Effect of the amino acid substituents on amide bond cleavage in N-acyl-alpha,alpha-dialkylglycine derivatives

Abstract

alpha,alpha-Dialkylglycines and their peptides have attracted considerable attention, as they show unique biological activities and very stable secondary structures. In previous work, we have reported that the amide bond at the C-terminus of a series of alpha,alpha-dialkylglycine derivatives such as Deg, Dpg, Dibg and Dbzg is labile to acid; cleavage was achieved by reaction with neat TFA, the products being obtained by aqueous work-up. We believe that an oxazolinonium-type intermediate (2) is involved in these reactions, as proposed by other authors. Now, we report the synthesis of a set of derivatives of Aib and Dbzg (1a-h) and preliminary results of accurate kinetic studies concerning their cleavage, having in mind to establish structure-reactivity relationships to evaluate the role of the various substituents on the reactivity of these compounds.