biostudies-literatureWinkler JDNCI NIH HHS9726-8https://www.ebi.ac.uk/biostudies/studies/S-EPMC3398804biostudies-literatureUnknown124(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 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.Journal of the American Chemical SocietyThe first total synthesis of (+/-)-ingenol.PMC3398804CA45686R01 CA040250CA40250Winkler JDJeon YTRouse MBGreaney MFHarrison SJfalseThe first total synthesis of (+/-)-ingenol.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.2002-01-01T00:00:00Z2002 Aug2025-04-18T16:16:07.167Z2019-03-27T00:55:42ZS-EPMC33988041217522910.1021/ja026600a