Total Synthesis and Stereochemical Reassignment of Mandelalide A

The total synthesis of the tunicate metabolite mandelalide A and the correction of its originally assigned stereochemistry are reported. Key features of the convergent, fully stereocontrolled route include the use of a Prins cyclization for the diastereoselective construction of the tetrahydropyran subunit, Rychnovsky-Bartlett cyclization for the preparation of the tetrahydrofuran moiety, Suzuki coupling, Horner-Wadsworth-Emmons macrocyclization, and glycosylation to append the L-rhamnose-derived pyranoside.