γ- and δ-Amino Acids: Synthetic Strategies and Relevant Applications

A.      Trabocchi; F.      Guarna; A.      Guarna

doi:10.2174/1385272054553631

Abstract

Over the years, γ and δamino acids have gathered much interest in drug discovery, especially in the peptidomimetic area. Much work on γamino acids has been focused towards the generation of γamino butyric acid (GABA) analogues, and the development of asymmetric approaches starting from unsaturated compounds, while few examples have been reported about carbohydrate-derived scaffolds as γamino acids. δAmino acids became of great importance as they have been selected as building blocks for backbone generation of peptide nucleic acid (PNA) structures. As further applications of δamino acids, carbohydrate research produced interesting examples of new δamino acids as building blocks for peptidomimetic design, and several reverse turn mimetics have been reported, too. Moreover, many studies have been concentrated on the conformational analysis of oligomeric sequences in analogy with β-peptides. This report is a description of relevant synthetic approaches to new γamino acids through the use of sugar chemistry and asymmetric synthesis, and to synthetic strategies for δamino acids, covering the area of carbohydrate chemistry, alkenebased chemistry, and asymmetric synthesis.

Keywords: peptidomimetics, pna monomers, michael addition, meldrums acid, dibah, krapcho decarboxylation, foldamer design, other gaba analogues, neuraminic acid