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

被引：66

作者：

Gunatilaka, AAL

Ramdayal, FD

Sarragiotto, MH

Kingston, DGI ^{[1
]}

Sackett, DL

Hamel, E

机构：

[1] Virginia Polytech Inst & State Univ, Dept Chem, Blacksburg, VA 24061 USA

[2] NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment & Diag, Fred Hutchinson Canc Res Ctr, Frederick, MD 21702 USA

来源：

JOURNAL OF ORGANIC CHEMISTRY | 1999年 / 64卷 / 08期

关键词：

D O I：

10.1021/jo982095h

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

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.

引用

页码：2694 / 2703

页数：10

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