Mimicry of the Backbone and Side-Chain Geometry of Peptide Turns: Synthesis of Novel 4-Substituted Indolizidin-9-one Amino Acids

Abstract

Indolizidinone amino acids have served as ß-turn mimics for exploring conformation-activity relationships in natural peptides [1]. Focus has been particularly placed on mirnicry of peptides containing aromatic residues within turn regions because of their importance in various recognition events. For example, 4- and 7-benzyl-indolizidin-2-one amino acid analogs 1 and 2 have been respectively used to synthesize ligands of the tachykinin and opioid receptors [2,3]. Similarly, indolizidin-9-one amino acid 3 has served in the synthesis of potent gramicidin S antibiotic peptides [4]. Interested in expanding the variety of indolizidinone amino acids possessing aromatic side-chains, we have now developed a new means for synthesizing 4-aryl-indolizidin-9-one amino acids 4.