Abstract
A convergent stereoselective synthesis of (4R,15R,16R,21S)- and (4R,15S,16S,21S)-rollicosin and squamostolide was accomplished via a Pd-catalyzed cross-coupling reaction. The inhibitory activity of these compounds was examined with bovine heart mitochondrial NADH-ubiquinone oxidoreductase. These compounds showed a remarkably weak inhibitory activity compared to ordinary acetogenins such as bullatacin. Our results indicate that to maintain potent inhibitory effect, the hydroxylated lactone cannot substitute for the hydroxylated mono- or bis-THF rings with a long alkyl chain that can be seen in ordinary acetogenins.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkynes / chemical synthesis*
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Alkynes / chemistry
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Alkynes / pharmacology*
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Animals
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Cattle
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Electron Transport Complex I / antagonists & inhibitors*
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Electron Transport Complex I / metabolism
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Furans / chemical synthesis*
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Furans / chemistry
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Furans / pharmacology*
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Isomerism
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Lactones / chemical synthesis*
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Lactones / chemistry
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Lactones / pharmacology*
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Magnetic Resonance Spectroscopy
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Mitochondria, Heart / drug effects*
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Mitochondria, Heart / enzymology*
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Molecular Structure
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Structure-Activity Relationship
Substances
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Alkynes
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Enzyme Inhibitors
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Furans
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Lactones
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rollicosin
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squamostolide
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Electron Transport Complex I