Total synthesis of (-)-pseudolaric acid B.
We report the enantioselective synthesis of pseudolaric acid B (1a), a diterpene acid isolated from the bark of Pseudolarix kaempferi Gordon, which displays interesting antifungal, antifertility, and cytotoxic activity against multidrug resistant cell lines. Our synthesis utilizes a highly efficient metal-catalyzed [5 + 2] vinylcyclopropane-alkyne intramolecular cycloaddition to construct the polyhydroazulene core of the natural product. Elaboration to the tricyclic scaffold of the pseudolaric acids was completed with an intramolecular alkoxycarbonyl radical cyclization to form the quaternary center and a highly diastereoselective cerium acetylide addition to a methyl ketone for introduction of the acid side chain.
Trost
Barry M
BM
Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA. bmtrost@stanford.edu
Waser
Jerome
J
Meyer
Arndt
A
D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry; D015394:Molecular Structure
D004224:Diterpenes; D006859:Hydrogen; C058391:pseudolaric acid B