A Flexible Three-Component Synthesis of Novel δ-Amino Acids Incorporating an Imidazo[1,2-a]pyridine Backbone

Abstract

Methyl 2-trimethylsiloxycyclopropanecarboxylates 1, 2-aminopyridine (2), and isonitriles 3 combine in a one-pot reaction to provide a series of novel δ-amino acids 4 incorporating an imidazo[1,2-a]pyridine backbone. Scope and limitations of this new three-component synthesis were investigated. Several reactions of compounds 4 affording suitably protected derivatives such as 5, 6 and 9 were performed to allow couplings with L-alanine derivatives. The expected peptides 11 and 12 were obtained by standard coupling reactions with excellent or moderate yield. Cyanide-catalyzed reactions converted compounds 4e and 4h into tricyclic δ-lactams 10e and 10h in very good yields.