Abstract
The isolation, characterization, and total synthesis of the macrocyclic polyene mangrolide D is reported. A 16-step total synthesis relies on robust Suzuki and ring-closing metathesis reactions, and an iron-catalyzed hydroazidation of an exomethylene substituted tetrahydropyran as a key step for the synthesis of the appended 4- epi-vancosamine sugar. Although mangrolide D did not display antibiotic activity, this work should prove enabling toward the synthesis of the antitubercular tiacumicins which display a virtually identical macrocyclic backbone.
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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Anti-Bacterial Agents / chemical synthesis
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Anti-Bacterial Agents / chemistry*
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Anti-Bacterial Agents / pharmacology
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Aquatic Organisms
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Bacillus subtilis / drug effects
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Catalysis
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Cycloaddition Reaction
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Glycosylation
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Hexosamines / chemical synthesis
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Macrolides / chemical synthesis
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Macrolides / chemistry*
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Macrolides / pharmacology
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Polyenes / chemical synthesis
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Polyenes / chemistry*
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Polyenes / pharmacology
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Pseudomonas aeruginosa / drug effects
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Stereoisomerism
Substances
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Anti-Bacterial Agents
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Hexosamines
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Macrolides
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Polyenes
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vancosamine