Abstract
A modified synthetic route to combretastatin D-2 (5) was devised in order to further evaluate its biological activity, for its conversion to phosphate prodrugs (25-28), and as a route to obtaining dihydro-combretastatin D-2 (42). A parallel first total synthesis of dihydro-combretastatin D-2 was completed, proceeding from a saturated 3-phenylpropionic ester intermediate via the Ullmann biaryl ether reaction (39-41). In contrast to the cancer cell growth inhibitory activity exhibited by combretastatin D-2, relatively minor structural modifications (41, 42) caused elimination of those properties.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents, Phytogenic / chemical synthesis*
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Antineoplastic Agents, Phytogenic / chemistry
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Antineoplastic Agents, Phytogenic / pharmacology*
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Bibenzyls / chemical synthesis*
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Bibenzyls / chemistry
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Bibenzyls / pharmacology*
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Crystallography, X-Ray
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Drug Design
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Drug Screening Assays, Antitumor
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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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Phenyl Ethers / chemical synthesis*
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Phenyl Ethers / chemistry
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Phenyl Ethers / pharmacology*
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Prodrugs / chemical synthesis*
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Prodrugs / chemistry
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Prodrugs / pharmacology*
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Structure-Activity Relationship
Substances
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Antineoplastic Agents, Phytogenic
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Bibenzyls
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Lactones
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Phenyl Ethers
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Prodrugs
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combretastatin D2
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combretastatin