Abstract
Spliceostatin A is a potent inhibitor of spliceosomes and exhibits excellent anticancer activity against multiple human cancer cell lines. We describe here the design and synthesis of a stable cyclopropane derivative of spliceostatin A. The synthesis involved a cross-metathesis or a Suzuki cross-coupling reaction as the key step. The functionalized epoxy alcohol ring was constructed from commercially available optically active tri- O-acetyl-d-glucal. The biological properties of the cyclopropyl derivative revealed that it is active in human cells and inhibits splicing in vitro comparable to spliceostatin A.
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 / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Cyclopropanes / chemical synthesis*
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Cyclopropanes / chemistry
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Cyclopropanes / pharmacology
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HeLa Cells
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Humans
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Molecular Structure
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Pyrans / chemical synthesis*
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Pyrans / chemistry
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Pyrans / pharmacology
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Spiro Compounds / chemical synthesis*
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Spiro Compounds / chemistry
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Spiro Compounds / pharmacology
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Stereoisomerism
Substances
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Antineoplastic Agents
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Cyclopropanes
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Pyrans
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Spiro Compounds
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spliceostatin A