Journal of the American Chemical Society, Vol.133, No.17, 6549-6552, 2011
Enantioselective Total Synthesis of (+)-Gliocladine C: Convergent Construction of Cyclotryptamine-Fused Polyoxopiperazines and a General Approach for Preparing Epidithiodioxopiperazines from Trioxopiperazine Precursors
A concise second-generation total synthesis of the fungal-derived alkaloid (+)-gliocladin C (11) in 10 steps and 1196 overall yield from isatin is reported. In addition, the epipolythiodioxopiperazine (ETP) natural product (+)-gliocladine C (6) has been prepared in six steps and 2996 yield from the di-(tert-butoxycarbonyl) precursor of 11. The total synthesis of 6 constitutes the first total synthesis of an ETP natural product containing a hydroxyl substituent adjacent to a quaternary carbon stereocenter in the pyrrolidine ring.