Total and semisynthesis and in vitro studies of both enantiomers of 20-fluorocamptothecin

Raghuram S. Tangirala, Rachel Dixon, Danzhou Yang, Attila Ambrus, Smitha Antony, Keli Agama, Yves Pommier, Dennis P. Curran

Research output: Contribution to journalArticle

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4736-4740
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume15
Issue number21
DOIs
StatePublished - Nov 1 2005

Keywords

  • Camptothecin
  • Isonitrile radical annulation
  • Topoisomerase I

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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  • Cite this

    Tangirala, R. S., Dixon, R., Yang, D., Ambrus, A., Antony, S., Agama, K., Pommier, Y., & Curran, D. P. (2005). Total and semisynthesis and in vitro studies of both enantiomers of 20-fluorocamptothecin. Bioorganic and Medicinal Chemistry Letters, 15(21), 4736-4740. https://doi.org/10.1016/j.bmcl.2005.07.074