Abstract
Both enantiomers of 20-fluorocamptothecin and the racemate have been prepared by total synthesis. The (R)-enantiomer is essentially inactive in a topoisomerase-I/DNA assay, while the (S)-enantiomer is much less active than (20S)-camptothecin. The lactone ring of 20-fluorocamptothecin hydrolyzes more rapidly than that of camptothecin in PBS. The results provide insight into the role of the 20-hydroxy group in the binding of camptothecin to topoisomerase-I and DNA.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology
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Camptothecin / analogs & derivatives*
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Camptothecin / chemical synthesis
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Camptothecin / chemistry
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Camptothecin / 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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Hydrogen Bonding
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Hydrolysis
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Kinetics
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Stereoisomerism
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Structure-Activity Relationship
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Topoisomerase I Inhibitors*
Substances
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20-fluorocamptothecin
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Antineoplastic Agents
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Enzyme Inhibitors
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Topoisomerase I Inhibitors
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Camptothecin