VERSATILE FMOC-ACETAL MERRIFIELD RESINS: SYNTHESES OF BICYCLIC LACTAMS & LACTONES

Abstract

The preparation of Merrifield resins 5, which represent versatile intermediates in the syntheses of lactones, lactams, and bicyclic, tricyclic, and tetracyclic scaffolds, is described. The presence of Fmoc and acetal protecting groups allows for the eventual incorporation of ozone-labile groups at R2 (as in III) such as alkenes, alkynes, electron-rich aromatics and pi-excessive heterocycles whereas the previously reported route can only accommodate ozone-compatible groups. An extension of the current methodology to include bicyclic lactams, which features elaboration at each of R1, R2, and R3 of III including fragment condensation examples 10a-c, is described. In all cases separation and characterization of two of the four possible diastereomers was achieved. Using 2-D NMR methods the relative configuration of the two diastereomers is being established. Structures such as III are of interest since the thiazabicycloalkane ring system is a known bioactive scaffold that mimics the beta-turn (reverse turn) in polypeptides and proteins.