Concerning the antileukemic agent jatrophatrione: the first total synthesis of a [5.9.5] tricyclic diterpene.
The highly functionalized [5.9.5] tricyclic framework resident in jatrophatrione (1) has been synthesized. The route begins with the tandem anionic oxy-Cope rearrangement/methylation/transannular ene cyclization of 5 and subsequent introduction of a conjugated enone double bond. Hydroxyl-directed 1,4-reduction of this functionality in 6 with LiAlH4/CuI/HMPA/THF sets the stage for the implementation of a Grob fragmentation and rapid generation of 8. Stereocontrolled intramolecular hydrosilylation allows for the subsequent introduction of a cyclic carbonate as in 11. This intermediate undergoes a remarkably smooth Treibs reaction to generate 12, thus serving as a pivotal step for making 1 available five steps later.
Paquette
Leo A
LA
Evans Chemical Laboratories, The Ohio State University, Columbus, Ohio 43210, USA. paquette.1@osu.edu
Yang
Jiong
J
Long
Yun Oliver
YO
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis*; D004224:Diterpenes / Q000138:chemical synthesis*; D019665:Euphorbiaceae / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry
D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; C012392:jatrophatrione