Thionium ion initiated medium-sized ring formation: the total synthesis of asteriscunolide D.

Barry M Trost, Aaron C Burns, Mark J Bartlett, Thomas Tautz, Andrew H Weiss

Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA. bmtrost@stanford.edu

Journal of the American Chemical Society 2012 Jan 25

filter terms:

The first synthesis of the biologically active humulene natural product asteriscunolide D has been accomplished in nine steps without the use of protecting groups. The challenging 11-membered ring was forged via a diastereoselective thionium ion initiated cyclization, which constitutes a formal aldol disconnection to form a strained macrocycle. A stereospecific thioether activation-elimination protocol was developed for selective E-olefin formation, thus providing access to the most biologically active asteriscunolide. The absolute stereochemical configuration was established by the Zn-ProPhenol catalyzed enantioselective addition of methyl propiolate to an aliphatic aldehyde to afford a γ-hydroxy propiolate as a handle for butenolide formation via Ru-catalyzed alkene-alkyne coupling. © 2012 American Chemical Society

Citation

Barry M Trost, Aaron C Burns, Mark J Bartlett, Thomas Tautz, Andrew H Weiss. Thionium ion initiated medium-sized ring formation: the total synthesis of asteriscunolide D. Journal of the American Chemical Society. 2012 Jan 25;134(3):1474-7