title: Catalysis-based total synthesis of putative mandelalide A.
abstract: A concise synthesis of the putative structure assigned to the highly cytotoxic marine macrolide mandelalide A (1) is disclosed. Specifically, an iridium-catalyzed two-directional Krische allylation and a cobalt-catalyzed carbonylative epoxide opening served as convenient entry points for the preparation of the major building blocks. The final stages feature the first implementation of terminal-acetylene metathesis into natural product synthesis, which is remarkable as this class of substrates was beyond reach until very recently; key to success was the use of the highly selective molybdenum alkylidyne complex 42 as the catalyst. Although the constitution and stereochemistry of the synthetic samples are unambiguous, the spectra of 1 as well as of 11-epi-1 deviate from those of the natural product, which implies a subtle but deep-seated error in the original structure assignment.
authors.affiliation: Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr (Germany).
authors.forename: Jens
authors.initials: J
authors.lastname: Willwacher
authors.forename: Alois
authors.initials: A
authors.lastname: Fürstner
mesh_terms: D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D008982:Molybdenum / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D001688:Biological Products; D018942:Macrolides; C000589407:mandelalide A; D008982:Molybdenum
keywords: alkyne metathesis; molybdenum; natural products; structure elucidation; total synthesis