title: Polyketide construction via hydrohydroxyalkylation and related alcohol C-H functionalizations: reinventing the chemistry of carbonyl addition.
abstract: Despite the longstanding importance of polyketide natural products in human medicine, nearly all commercial polyketide-based drugs are prepared through fermentation or semi-synthesis. The paucity of manufacturing routes involving de novo chemical synthesis reflects the inability of current methods to concisely address the preparation of these complex structures. Direct alcohol C-H bond functionalization via"C-C bond forming transfer hydrogenation" provides a powerful, new means of constructing type I polyketides that bypasses stoichiometric use of chiral auxiliaries, premetallated C-nucleophiles, and discrete alcohol-to-aldehyde redox reactions. Using this emergent technology, total syntheses of 6-deoxyerythronolide B, bryostatin 7, trienomycins A and F, cyanolide A, roxaticin, and formal syntheses of rifamycin S and scytophycin C, were accomplished. These syntheses represent the most concise routes reported to any member of the respective natural product families.
authors: University of Texas at Austin, Department of Chemistry and Biochemistry, 105 E 24th St., Welch Hall A5300, Austin, TX 78712-1165, USA. mkrische@mail.utexas.edu.
authors: Anne-Marie R
authors: AM
authors: Dechert-Schmitt
authors: Daniel C
authors: DC
authors: Schmitt
authors: Xin
authors: X
authors: Gao
authors: Takahiko
authors: T
authors: Itoh
authors: Michael J
authors: MJ
authors: Krische
mesh_terms: D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis / Q000737:chemistry; D054713:Bryostatins / Q000138:chemical synthesis / Q000737:chemistry; D002384:Catalysis; D004917:Erythromycin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D006865:Hydrogenation; D018942:Macrolides / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D061065:Polyketides / Q000138:chemical synthesis* / Q000737:chemistry; D012294:Rifamycins / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D001688:Biological Products; D019086:Bridged Bicyclo Compounds, Heterocyclic; D054713:Bryostatins; D018942:Macrolides; D061065:Polyketides; D012294:Rifamycins; C475531:bryostatin 7; C480363:roxaticin; C449042:scytophycin C; C034277:6-deoxyerythronolide B; D004917:Erythromycin; C023808:rifamycin SV; C032779:rifamycin S