An improved approach for the synthesis of alfa,alfa-dialkyl glycine derivatives by the Ugi-Passerini reaction

Abstract

A general and simple strategy for routine peptide synthesis with alfa,alfa-dialkyl glycines taking advantage of the four-component Ugi-Passerini reaction is presented. The isonitrile required for the reaction can be relatively simple and its selection based on cost, as the group it generates is easily removed under acidic conditions; in addition, this removal is not visibly affected by the bulkiness of the alfa-alkyl groups. Being a good leaving group from the N-terminal amino group of the amino acid, 4-methoxybenzyl was the choice for the amine component of the reaction. The method is illustrated with the synthesis of a series of acyl derivatives of several alfa,alfa-dialkyl glycines. The preparation of the latter compounds is also reported.