Abstract
The first synthesis of the racemate of terpendole E, a specific inhibitor of the mitotic kinesin Eg5, has been achieved from a known tricyclic dihydroxy ketone by a 13-step sequence that involves diastereoselective installation of its C3 quaternary stereocenter via a cyclopropyl ketone intermediate and Pd-mediated two-step construction of the indole ring moiety as the key transformations.
Keywords:
antimitotic; indole diterpene; kinesin spindle protein; terpendole; total synthesis.
MeSH terms
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Diterpenes / chemical synthesis*
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Diterpenes / pharmacology
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology
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Humans
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Indoles / chemical synthesis
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Indoles / chemistry*
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Indoles / pharmacology
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Ketones / chemistry*
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Kinesins / antagonists & inhibitors
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Kinesins / metabolism
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Microtubules / drug effects
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Microtubules / metabolism
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Mitosis / drug effects
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Spindle Apparatus / drug effects
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Stereoisomerism
Substances
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Diterpenes
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Enzyme Inhibitors
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Indoles
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KIF11 protein, human
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Ketones
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terpendole E
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Kinesins