title: Total synthesis of an exceptional brominated 4-pyrone derivative of algal origin: an exercise in gold catalysis and alkyne metathesis.
abstract: A concise approach to the algal metabolite 1 is described, which also determines the previously unknown stereostructure of this natural product. Compound 1 is distinguished by a rare brominated 4-pyrone nucleus linked as a ketene-acetal to a polyunsaturated macrocyclic scaffold comprising an extra homoallylic bromide entity. The synthesis of 1 is based on the elaboration and selective functionalization of the linear precursor 23 endowed with no less than six different sites of unsaturation including the highly enolized oxo-alkanoate function. Key to success was the formation of the 2-alkoxy-4-pyrone ring by a novel gold-catalyzed transformation which engages only the acetylenic β-ketoester substructure of 23 but leaves all other π-bonds untouched. The synthesis was completed by a ring-closing alkyne metathesis to forge the signature cycloalkyne motif of 1 followed by selective bromination of the ketene-acetal site in the resulting product 27 without touching the skipped diene-yne substructure resident within the macrocyclic tether.
authors.affiliation: Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr (Germany).
authors.forename: Laura
authors.initials: L
authors.lastname: Hoffmeister
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Fukuda
authors.forename: Gerit
authors.initials: G
authors.lastname: Pototschnig
authors.forename: Alois
authors.initials: A
authors.lastname: Fürstner
mesh_terms: D000080:Acetals / Q000737:chemistry; D000480:Alkynes / Q000737:chemistry; D002384:Catalysis; D018360:Crystallography, X-Ray; D003500:Cyclization; D005030:Ethylenes / Q000737:chemistry; D006046:Gold / Q000737:chemistry; D054879:Halogenation; D007659:Ketones / Q000737:chemistry; D008968:Molecular Conformation; D008982:Molybdenum / Q000737:chemistry; D011753:Pyrones / Q000138:chemical synthesis / Q000737:chemistry*; D000461:Rhodophyta / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D000080:Acetals; D000480:Alkynes; D005030:Ethylenes; D007659:Ketones; D011753:Pyrones; D006046:Gold; D008982:Molybdenum; C008223:ketene
keywords: alkyne metathesis; biosynthesis; gold; heterocycles; molybdenum; natural products