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

doi:10.1021/jo982095h

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 language	English (US)
Pages (from-to)	2694-2703
Number of pages	10
Journal	Journal of Organic Chemistry
Volume	64
Issue number	8
DOIs	https://doi.org/10.1021/jo982095h
State	Published - Apr 16 1999

ASJC Scopus subject areas

Organic Chemistry

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title = "Synthesis and biological evaluation of novel paclitaxel (Taxol) D-ring modified analogues",

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.",

author = "Gunatilaka, {A. A.Leslie} and Ramdayal, {Frank D.} and Sarragiotto, {Maria H.} and Kingston, {David G.I.} and Sackett, {Dan L.} and Ernest Hamel",

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AU - Gunatilaka, A. A.Leslie

AU - Ramdayal, Frank D.

AU - Sarragiotto, Maria H.

AU - Kingston, David G.I.

AU - Sackett, Dan L.

AU - Hamel, Ernest

PY - 1999/4/16

Y1 - 1999/4/16

N2 - 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.

AB - 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.

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

Abstract

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