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.

amino acids - cyclopropanes - pyridines - lactams - peptides

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Atomic coordinates and further crystallographic details have been deposited at the Cambridge Crystallographic Data Centre, deposition number CCDC 601760, and copies of this data can be obtained in application to CCDC, University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, UK (fax: [phone]; e-mail: [e-mail]).