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dc.contributor.authorNicolaou, K.C.
Hale, Christopher R.H.
Nilewski, Christian
Ioannidou, Heraklidia A.
ElMarrouni, Abdelatif
Nilewski, Lizanne G.
Beabout, Kathryn
Wang, Tim T.
Shamoo, Yousif
dc.date.accessioned 2014-09-12T17:46:11Z
dc.date.available 2014-09-12T17:46:11Z
dc.date.issued 2014
dc.identifier.citation Nicolaou, K.C., Hale, Christopher R.H., Nilewski, Christian, et al.. "Total Synthesis of Viridicatumtoxin B and Analogues Thereof: Strategy Evolution, Structural Revision, and Biological Evaluation." Journal of the American Chemical Society, 136, no. 34 (2014) American Chemical Society: 12137-12160. http://dx.doi.org/10.1021/ja506472u.
dc.identifier.urihttps://hdl.handle.net/1911/77175
dc.description.abstract The details of the total synthesis of viridicatumtoxin B (1) are described. Initial synthetic strategies toward this intriguing tetracycline antibiotic resulted in the development of key alkylation and Lewis acid-mediated spirocyclization reactions to form the hindered EF spirojunction, as well as Michael-Dieckmann reactions to set the A and C rings. The use of an aromatic A-ring substrate, however, was found to be unsuitable for the introduction of the requisite hydroxyl groups at carbons 4a and 12a. Applying these previous tactics, we developed stepwise approaches to oxidize carbons 12a and 4a based on enol- and enolate-based oxidations, respectively, the latter of which was accomplished after systematic investigations that revealed critical reactivity patterns. The herein described synthetic strategy resulted in the total synthesis of viridicatumtoxin B (1), which, in turn, formed the basis for the revision of its originally assigned structure. The developed chemistry facilitated the synthesis of a series of viridicatumtoxin analogues, which were evaluated against Gram-positive and Gram-negative bacterial strains, including drug-resistant pathogens, revealing the first structure-activity relationships within this structural type.
dc.language.iso eng
dc.publisher American Chemical Society
dc.rights Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
dc.title Total Synthesis of Viridicatumtoxin B and Analogues Thereof: Strategy Evolution, Structural Revision, and Biological Evaluation
dc.type Journal article
dc.contributor.funder National Institutes of Health
dc.contributor.funder Skaggs Institute of Research
dc.contributor.funder Cancer Prevention and Research Institute of Texas
dc.contributor.funder Welch Foundation
dc.citation.journalTitle Journal of the American Chemical Society
dc.citation.volumeNumber 136
dc.citation.issueNumber 34
dc.type.dcmi Text
dc.identifier.doihttp://dx.doi.org/10.1021/ja506472u
dc.identifier.pmcid PMC4210137
dc.identifier.pmid 25317739
dc.identifier.grantID AI055475 (National Institutes of Health)
dc.identifier.grantID AI080714 (National Institutes of Health)
dc.type.publication publisher version
dc.citation.firstpage 12137
dc.citation.lastpage 12160


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