Asymmetric total synthesis of the indole alkaloid cyclopiazonic acid and first structure activity data

The indole alkaloid cz-cyclopiazonic acid (CPA) is one of the few known inhibitors of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) besides the terpenoids thapsigargin and artemisinin. We report here the first asymmetric total synthesis of cyclopiazonic acid by a modification of the Knight synthesis, currently the most efficient route to CPA. First structure activity data of CPA derivatives and stereoisomers are presented and will be discussed in connection with the published crystal-structures of CPA SERCA complexes. (C) 2011 Elsevier Ltd. All rights reserved.