Abstract
The total synthesis and biological evaluation of neopeltolide and analogs are reported. The key bond-forming step utilizes a Lewis acid-catalyzed intramolecular macrocyclization that installs the tetrahydropyran ring and macrocycle simultaneously. Independent of each other, neither the macrolide nor the oxazole side chain substituents of neopeltolide can inhibit the growth of cancer cell lines. The biological data of the analogs indicate that alterations to either the ester side chain or the stereochemistry of the macrolide result in a loss of biological activity.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Alcohols / chemistry
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Animals
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Biological Products / chemical synthesis*
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Biological Products / chemistry
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Biological Products / pharmacology*
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Carboxylic Acids / chemistry
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cyclization
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Humans
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Inhibitory Concentration 50
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Macrolides / chemical synthesis
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Macrolides / chemistry*
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Macrolides / pharmacology*
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Oceans and Seas
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Oxazoles / chemistry
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Structure-Activity Relationship
Substances
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Alcohols
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Biological Products
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Carboxylic Acids
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Macrolides
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Oxazoles
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neopeltolide