Total synthesis of (-)-microcarpalide, a novel microfilament disrupting metabolite

The stereoselective total synthesis of (-)-microcarpalide, a recently discovered 10-membered lactone of fungal origin displaying a remarkable disrupting action on actin micro. laments, was accomplished by using ring-closing metathesis (RCM) as the key step for the formation of the medium-sized ring. The diene ester required for the macrocyclization reaction was assembled via DCC-mediated esterification of two suitable partners, each bearing a terminal alkene group. The alcohol fragment was synthesized from n-bromohexane through a seven-step sequence entailing two consecutive stereoselective homologations of chiral boronic esters as strategic transformations for the sequential insertion of the two stereocentres with the final S absolute configuration, using (+)-pinanediol as the chiral director; final elaboration to the desired C-11 framework envisaged treatment with an allyl Grignard reagent and oxidative cleavage of the boronic scaffold. In contrast, the acidic fragment was prepared in ten steps from D-tartaric acid, whose C-4 backbone was elongated to the required C-7 skeleton by means of two distinct Swern-Wittig oxidation - homologation sequences.