Nα-2-(4-Nitrophenylsulfonyl)ethoxycarbonyl (Nsc) as an amino-protecting group and its application for peptide synthesis

Abstract

The discovery of ester and urethane protective groups cleavable by base-promoted elimination under aprotic conditions appeared to be a substantial contribution to the recent progress of the peptide synthesis. The most prominent representative of this class, Fmoc group, has played a pivotal role in the development of SPPS. The remarkable stability of the Fmoc group towards acids and its mild cleavage by organic bases in aprotic solvents provide its compatibility with the acid-labile tBu group, and secure a very broad application of the Fmoc/tBu-methodology in the modern automated SPPS. Despite of the revealed drawbacks, the Fmoc group has remained for many years virtually a sole baselabile -protection employed in the routine peptide synthesis. In our early studies [1,2], we found that 2-alkyland 2-arylsulfonylethyl esters and urethanes can be cleaved not only by aqueous alkaline treatment, but also by strong organic bases in a manner very similar to that used for the cleavage of analogous 9fluorenylmethyl (Fm) derivatives. Kinetic and mechanistic studies, which were performed on a series of model sulfonylethyl urethanes [2], showed that the mechanism of their cleavage by such bases as DBU or piperidine in DMF was essentially the same as that of the Fmoc group. Moreover, the cleavage rate was strongly dependent on the nature of arylic substituents. These findings led further to the development of Nsc as a new base-labile protecting group for SPPS [3]. The present report is a brief review of the properties of the Nsc-group and its applications for peptide synthesis.