Synthesis and biological evaluation of novel paclitaxel (Taxol) D-ring modified analogues

A. A.Leslie Gunatilaka, Frank D. Ramdayal, Maria H. Sarragiotto, David G.I. Kingston, Dan L. Sackett, Ernest Hamel

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Abstract

The semisynthesis and biological activity of paclitaxel (Taxol) analogues in which the oxygen atom in ring D is substituted by a sulfur or a selenium atom is presented. These derivatives were synthesized and tested in order to make more transparent the role of the oxetane ring in the biological activity of paclitaxel. The sulfur derivatives were found to be less active than paclitaxel in biological assays, while the selenium derivative could not be converted to its 4-acyl analogue. The results with the sulfur analogues suggest that the oxygen atom in the oxetane ring plays an important role in the mechanism by which paclitaxel exhibits its anticancer activity.

Original languageEnglish (US)
Pages (from-to)2694-2703
Number of pages10
JournalJournal of Organic Chemistry
Volume64
Issue number8
DOIs
StatePublished - Apr 16 1999

ASJC Scopus subject areas

  • Organic Chemistry

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    Gunatilaka, A. A. L., Ramdayal, F. D., Sarragiotto, M. H., Kingston, D. G. I., Sackett, D. L., & Hamel, E. (1999). Synthesis and biological evaluation of novel paclitaxel (Taxol) D-ring modified analogues. Journal of Organic Chemistry, 64(8), 2694-2703. https://doi.org/10.1021/jo982095h