A stereoselective synthesis via a 5-exo-trig cyclisation of trans-2-oxohexahydro-2H-furo[3,2-b]pyrroles (pyrrolidine-trans-lactones)—potent, novel elastase inhibitors

Abstract

trans-2-Oxohexahydro-2H-furo[3,2-b]pyrroles (such as 2) are conformationally strained 5,5-fused ring systems and are potent human neutrophil elastase (HNE) inhibitors. A stereoselective synthesis is described based on intramolecular 5-exo-trig cyclisations of aldehyde acrylates 4 and 5 mediated by samarium(II) iodide to give predominantly trans-products 9 and 15. The n-propyl group in 15 is also generated with stereoselectivity for the desired β-isomer.