Abstract
An efficient synthesis of an exo-enone analogue (5) of resorcylic acid lactone (RAL), natural product LL-Z1640-2 (1), has been achieved using a Ni-catalysed regioselective reductive coupling macrocyclisation of an alkyne-aldehyde as a key step. The synthetic route is significantly shorter than those for the natural product and avoids the isomerisation problem of the cis-double bond in the molecule. The preliminary biological evaluation showed that the exo-enone analogue is a potent inhibitor of several important kinases relevant to cancer drug development.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Dose-Response Relationship, Drug
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Ketones / chemical synthesis
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Ketones / chemistry
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Ketones / pharmacology*
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Lactones / chemical synthesis
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Lactones / chemistry
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Lactones / pharmacology*
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Molecular Structure
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Phosphotransferases / antagonists & inhibitors*
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Phosphotransferases / metabolism
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology*
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Structure-Activity Relationship
Substances
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Ketones
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LL Z1640-2
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Lactones
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Protein Kinase Inhibitors
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Phosphotransferases