Ring-closing metathesis: a powerful tool for the synthesis of simplified salicylihalamide-based V-ATPase inhibitors

Based on our synthetic strategy developed for the total synthesis of the macrocyclic salicylate natural product salicylihalamide, we describe herein the synthesis of a series of simplified salicylihalamide-based analogs. Alterations in the aromatic fragment, the macrolactone scaffold and side-chain were evaluated for in vitro inhibition of V-ATPase activity and human tumor cell growth.