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

The indole alkaloid α-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.

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