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dc.contributor.authorNicolaou, K.C.
Heretsch, Philipp
Nakamura, Tsuyoshi
Rudo, Anna
Murata, Michio
Konoki, Keiichi
dc.date.accessioned 2014-12-05T18:35:05Z
dc.date.available 2014-12-05T18:35:05Z
dc.date.issued 2014
dc.identifier.citation Nicolaou, K.C., Heretsch, Philipp, Nakamura, Tsuyoshi, et al.. "Synthesis and Biological Evaluation of QRSTUVWXYZA' Domains of Maitotoxin." Journal of the American Chemical Society, 136, no. 46 (2014) American Chemical Society: 16444-16451. http://dx.doi.org/10.1021/ja509829e.
dc.identifier.urihttps://hdl.handle.net/1911/78583
dc.description.abstract The synthesis of QRSTUVWXYZA′ domains 7, 8, and 9 of the highly potent marine neurotoxin maitotoxin (1), the largest secondary metabolite isolated to date, is described. The devised synthetic strategy entailed a cascade Takai–Utimoto ester olefination/ring closing metathesis to construct ring Y, a hydroxydithioketal cyclization/methylation sequence to cast ring X, a Horner–Wadsworth–Emmons coupling of WXYZA′ ketophosphonate 11 with QRSTU aldehyde 12 to form enone 10, and a reductive hydroxyketone ring closure to forge ring V. 2D NMR spectroscopic analysis and comparison of 13C chemical shifts with those of the corresponding carbons of maitotoxin revealed close similarities supporting the originally assigned structure of this region of the natural product. Biological evaluations of various synthesized domains of maitotoxin in this and previous studies from these laboratories led to fragment structure–activity relationships regarding their ability to inhibit maitotoxin-elicited Ca2+ influx in rat C6 glioma cells.
dc.language.iso eng
dc.publisher American Chemical Society
dc.rights This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by the American Chemical Society.
dc.title Synthesis and Biological Evaluation of QRSTUVWXYZA' Domains of Maitotoxin
dc.type Journal article
dc.contributor.funder Cancer Prevention Research Institute of Texas
dc.contributor.funder Welch Foundation
dc.contributor.funder Rice University
dc.contributor.funder National Institutes of Health
dc.contributor.funder Deutsche Akademie der Naturforscher Leopoldina
dc.contributor.funder Japan Science and Technology Agency
dc.citation.journalTitle Journal of the American Chemical Society
dc.contributor.org BioScience Research Collaborative
dc.citation.volumeNumber 136
dc.citation.issueNumber 46
dc.type.dcmi Text
dc.identifier.doihttp://dx.doi.org/10.1021/ja509829e
dc.identifier.pmid 25374117
dc.identifier.grantID postdoctoral fellowship (Deutsche Akademie der Naturforscher Leopoldina)
dc.identifier.grantID ERATO Murata Lipid Active Structure Project (Japan Science and Technology Agency)
dc.type.publication post-print
dc.citation.firstpage 16444
dc.citation.lastpage 16451


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