Synthesis of (±)-Hirsutene
Tandem Radical Approach to Linear Condensed Cyclopentanoids. Total Synthesis of (±)-Hirsutene.
J. Am. Chem. Soc. 1985;
Radical-Initiated Polyolefinic Cyclizations in Linear Triquinane Synthesis. Model Studies and Total Synthesis of (±)-Hirsutene.
17 September 2019 (online)
Hirsutene is a linear triquinane that was isolated from the fungi Coriolus consors in 1976. Its lack of heteroatomic functional groups along with the presence of four contiguous stereocenters and two quaternary carbon atoms render this condensed cyclopentanoid natural product challenging. In 1985, Curran and Rakiewicz reported an elegant synthesis of (±)-hirsutene employing a late-stage radical cyclization.
Accessed in two steps from the corresponding enone, acetate A was converted into lactone B by Ireland–Claisen rearrangement followed by phenylselenolactonization. Elimination, SN2′ reaction, and deprotection furnished carboxylic acid E. Further transformation led to iodoenyne H, which underwent 5-exo-trig/5-exo-dig radical cyclization cascade in the presence of AIBN/Bu3SnH to afford (±)-hirsutene.