title: Formal total synthesis of the algal toxin (-)-polycavernoside A.
abstract: A concise and largely catalysis-based approach to the potent algal toxin polycavernoside A (1) is described that intercepts a late-stage intermediate of a previous total synthesis; from there on, this challenging target can be reached in a small number of steps. Key to success was a sequence of a molybdenum-catalyzed ring-closing alkyne metathesis (RCAM) reaction to forge the macrocyclic frame, followed by a gold-catalyzed and strictly regioselective transannular hydroalkoxylation of the resulting cycloalkyne that allows the intricate oxygenation pattern of the macrolactone ring of 1 to be properly set. The required cyclization precursor 5 was assembled by the arguably most advanced fragment coupling process based on an Evans-Tishchenko redox esterification known to date, which was optimized to the extent that the precious coupling partners could be used in an almost equimolar ratio (6/7 1:1.3). The preparation of these building blocks features, inter alia, the power of the Sc(OTf)(3)-catalyzed Leighton crotylation as well as the superb selectivities of alkene cross metathesis, asymmetric keto-ester hydrogenation, and the Jacobsen epoxidation/epoxide resolution technologies.
authors: Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr, Germany.
authors: Lennart
authors: L
authors: Brewitz
authors: Josep
authors: J
authors: Llaveria
authors: Akira
authors: A
authors: Yada
authors: Alois
authors: A
authors: Fürstner
mesh_terms: D000475:Alkenes; D000480:Alkynes; D001685:Biological Factors; D002384:Catalysis; D003500:Cyclization; D004187:Disaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000475:Alkenes; D000480:Alkynes; D001685:Biological Factors; D004187:Disaccharides; D018942:Macrolides; C121303:polycavernoside A