New synthesis of β-(4-semicarbazido)carboxylic acid-based peptidomimetics and 3-amino-5,6-dihydrouracils via an amidoalkylation protocol

Abstract

A new approach to synthesize peptidomimetics consisting of α-aza-amino acid and β-amino acid residues, namely β-(4-semicarbazono)- and β-(4-semicarbazido)carboxylic acids, and their esters and hydrazides has been developed. The synthesis involves the amidoalkylation of diethyl malonate with 2-unsubstituted and 2-methyl-substituted 1-arylidene-4-(tosylmethyl)semicarbazides followed by hydrolysis, decarboxylation and substitution reactions. Acid-promoted cyclization of β-(4-semicarbazido)carboxylic acid hydrazides to derivatives of 3-amino-5,6-dihydrouracils has been also investigated. The conformational behavior of 3-acetylamino-5,6-dihydrouracils is discussed based on DFT calculations and dynamic NMR data.