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The first total synthesis of (+/-)-ingenol.

ABSTRACT: The first total synthesis of (+/-)-ingenol has been achieved. The key features of the synthesis include the use of a highly diastereoselective Michael reaction to fix the C-11 methyl stereochemistry and the incorporation of the dimethylcyclopropane via diastereoselective carbene addition to the Delta13,14 olefin. The intramolecular dioxenone photoaddition-fragmentation sequence leads to the establishment of the critical C-8/C-10 trans intrabridgehead stereochemistry, a central challenge in the synthesis of ingenanes. The completion of the synthesis proceeds using the C-6alpha hydroxymethyl group as the sole handle for oxidation of seven contiguous carbon centers.

SUBMITTER: Winkler JD

PROVIDER: S-EPMC3398804 | biostudies-literature | 2002 Aug

REPOSITORIES: biostudies-literature

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The first total synthesis of (+/-)-ingenol.

Winkler Jeffrey D JD Rouse Meagan B MB Greaney Michael F MF Harrison Sean J SJ Jeon Yoon T YT

Journal of the American Chemical Society 20020801 33

The first total synthesis of (+/-)-ingenol has been achieved. The key features of the synthesis include the use of a highly diastereoselective Michael reaction to fix the C-11 methyl stereochemistry and the incorporation of the dimethylcyclopropane via diastereoselective carbene addition to the Delta13,14 olefin. The intramolecular dioxenone photoaddition-fragmentation sequence leads to the establishment of the critical C-8/C-10 trans intrabridgehead stereochemistry, a central challenge in the s ...[more]

PMID: 12175229

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