The formal total synthesis of the (+)-salicylihalamides A and B is detailed, utilizing a chiral poolapproach to generate the three stereogenic centers and a ring-closing metathesis (RCM) for theformation of the macrocyclic ring structure. Starting from a known glucose-derived alcohol, theformal total synthesis was achieved in an efficient 13-step protocol in 26% overall yield. It wasfound that substitution at the remote phenolic group significantly influenced the ratio of the E-and Z-double bond products in the RCM step. The introduction of phenol protecting groups providedE-isomers preferentially and also enhanced the rates of the RCM reactions.
