Abstract
A stereoselective synthesis of 3'-O-((R,R,R)-trimethylsilatranyl)thymidine (R,R,R-1) and synthesis of 3'-O-silatranylthymidine (5) via an improved silatranylation procedure using tetrakis(dimethylamino)silane are reported. Diastereomeric mixture 1 showed more activity than R,R,R-1 or 5 in a primary anticancer screen against breast, CNS, and lung cell lines; demonstrating the import of the configuration and presence, respectively, of the silatrane methyl groups for growth inhibition.
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 / pharmacology
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Brain Neoplasms / drug therapy
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Brain Neoplasms / pathology
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Breast Neoplasms / drug therapy
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Breast Neoplasms / pathology
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Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis
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Bridged Bicyclo Compounds, Heterocyclic / pharmacology
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Cell Division / drug effects
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Drug Screening Assays, Antitumor
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Humans
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Lung Neoplasms / drug therapy
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Lung Neoplasms / pathology
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Organosilicon Compounds / chemical synthesis
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Organosilicon Compounds / pharmacology
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Sensitivity and Specificity
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Stereoisomerism
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Thymidine / analogs & derivatives*
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Thymidine / chemistry
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Thymidine / pharmacology
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Tumor Cells, Cultured
Substances
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Antineoplastic Agents
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Bridged Bicyclo Compounds, Heterocyclic
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Organosilicon Compounds
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silatrane
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Thymidine