Natural Product Reports 2014-04-01

Polyketide construction via hydrohydroxyalkylation and related alcohol C-H functionalizations: reinventing the chemistry of carbonyl addition.

Anne-Marie R Dechert-Schmitt, Daniel C Schmitt, Xin Gao, Takahiko Itoh, Michael J Krische

Index: Nat. Prod. Rep. 31(4) , 504-13, (2014)

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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.