Abstract
We report the details of the total synthesis of natural and non-natural jatropha-5,12-dienes. The successful tactic for the assembly of the strained trans-bicyclo[10.3.0]pentadecane scaffold employed a B-alkyl Suzuki-Miyaura cross-coupling for the formation of the C5/C6 double bond and a ring-closing metathesis for the construction of the C12/C13 double bond. The key step of the synthesis of the cyclopentane fragment, an uncatalyzed intramolecular carbonyl-ene reaction, was studied computationally by DFT calculations. The members of the ensemble of synthetic natural and non-natural jatrophanes were subsequently examined as modulators for the ABCB1, ABCG2, and ABCC1 efflux proteins, which are associated with multidrug resistance in cancer chemotherapy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / pharmacology
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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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Cell Line, Tumor
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Cross-Linking Reagents / chemistry*
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Crystallography, X-Ray
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Cyclization
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Cyclopentanes / chemistry*
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Diterpenes / chemical synthesis*
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Diterpenes / chemistry*
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Diterpenes / pharmacology
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Drug Resistance, Multiple / drug effects*
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Euphorbia / chemistry*
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Humans
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Lung Neoplasms / drug therapy*
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Lung Neoplasms / metabolism
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Magnetic Resonance Spectroscopy
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Molecular Structure
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Plant Extracts / chemical synthesis*
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Plant Extracts / chemistry*
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Plant Extracts / pharmacology
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Stereoisomerism
Substances
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Antineoplastic Agents
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Biological Products
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Cross-Linking Reagents
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Cyclopentanes
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Diterpenes
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Plant Extracts
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jatrophane