Abstract
A short practical synthesis of a new natural product based scaffold (6), based on antitrypanosomal and antimalarial compounds isolated from different Plakortis species is described. The scaffold contains a peroxide unit that is surprisingly stable to chemical manipulation elsewhere in the molecule, enabling it to be elaborated into a small library of derivatives. It is stable to ozonolysis, reductive work-up with dimethylsulfide and the Wittig reaction with stabilized phosphorus ylides. The scaffold along with its Wittig analogues has displayed low to sub-micro molar (0.2-3.3 μM) antitrypanosomal activity.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biological Factors / chemical synthesis
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Biological Factors / isolation & purification
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Biological Factors / pharmacology*
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Dioxanes / chemical synthesis
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Dioxanes / isolation & purification
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Dioxanes / pharmacology*
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Dose-Response Relationship, Drug
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Molecular Structure
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Parasitic Sensitivity Tests
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Plakortis / chemistry*
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Small Molecule Libraries
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Stereoisomerism
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Structure-Activity Relationship
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Trypanocidal Agents / chemical synthesis
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Trypanocidal Agents / isolation & purification
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Trypanocidal Agents / pharmacology*
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Trypanosoma brucei brucei / drug effects*
Substances
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Biological Factors
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Dioxanes
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Small Molecule Libraries
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Trypanocidal Agents