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 Ca 2+-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 synth...

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Bibliographic Details
Published in:	Tetrahedron Vol. 67; no. 17; pp. 3062 - 3070
Main Authors:	Beyer, W.R. Christian, Woithe, Katharina, Lüke, Bettina, Schindler, Michael, Antonicek, Horst, Scherkenbeck, Jürgen
Format:	Journal Article
Language:	English
Published:	Kidlington Elsevier Ltd 29-04-2011 Elsevier
Subjects:	Alicyclic compounds, terpenoids, prostaglandins, steroids Biological and medical sciences Chemistry Cyclopiazonic acid Enantioselective synthesis Exact sciences and technology Fundamental and applied biological sciences. Psychology Heterocyclic compounds Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives Heterocyclic compounds with only one n hetero atom and condensed derivatives Indole alkaloid Microbiology Mycology Organic chemistry Pathogenicity, host-agent relations, miscellaneous strains, epidemiology Preparations and properties SERCA Structure–activity data Terpenoids MOPS Ns TBDPS Structure–activity data SERCA ACN TfOH Cyclopiazonic acid Enantioselective synthesis DCM EGTA THF DBU DMF KHMDS Indole alkaloid Ts Endo stereoisomer Structure-activity data Enantioselectivity Molecular structure Nitrogen heterocycle Artemisinin Mycotoxin Oxygen heterocycle transporting ATPase Thapsigargin Alkaloid Structure activity relation Asymmetric synthesis Sesquiterpenes Chemical synthesis Terpenoid Enzyme Lactone Total synthesis Toxin Hydrolases Inhibitor Indole derivatives Ca Crystalline structure
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Summary:	The indole alkaloid α-cyclopiazonic acid (CPA) is one of the few known inhibitors of sarco( endo)plasmic reticulum Ca 2+-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. [Display omitted]
ISSN:	0040-4020 1464-5416
DOI:	10.1016/j.tet.2011.03.002