The 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.
Winkler
Jeffrey D
JD
Department of Chemistry, The University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. winkler@sas.upenn.edu
Rouse
Meagan B
MB
Greaney
Michael F
MF
Harrison
Sean J
SJ
Jeon
Yoon T
YT
D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D019906:Nuclear Magnetic Resonance, Biomolecular; D013237:Stereoisomerism
D004224:Diterpenes; C008125:ingenol