Synthesis of Diversely Functionalized Indolizidinones and Related Bicyclic Lactams Using Intramolecular Grubbs Olefin Metathesis and Dieckmann Condensation

Abstract

Bicyclic 1-aza-2-oxo ring systems with versatile functionality were synthesized from the Grubbs olefin metathesis of appropriate olefinic precursors, starting with l-pyroglutamic acid. The carbocyclization products were further functionalized utilizing the double bond or by enolate chemistry of the corresponding beta,gamma-unsaturated bicyclic lactam. In an alternative strategy, indolizidinones were synthesized by application of an intramolecular Dieckmann cyclization. A constrained peptidomimetic thrombin inhibitor was prepared from one of the bicyclic indolizidinones.