SYNTHESIS OF BENZO-FUSED, 7,5-FUSED AND 7,6-FUSED AZEPINONES AS CONFORMATIONALLY RESTRICTED DIPEPTIDE MIMETICS

Methodology for the generation of novel conformationally restricted di peptide mimetics 9 and 16 has been developed. The key step involved in tramolecular addition of an oxonium ion to the proximal indoline/tetra hydroquinoline aromatic ring. A dramatic difference in reactivity was observed in the formation of the 7,5- versus the 7,6-fused azepinone n uclei. Application of these mimetics in the synthesis of dual-acting A CE/NEP inhibitors 1 and 2 is described.