Diels-Alder/thiol-olefin co-oxygenation approach to antimalarials incorporating the 2,3-dioxabicyclo[3.3.1]nonane pharmacophore

被引：16

作者：

O'Neill, PM

Verissimo, E

Ward, SA

Davies, J

Korshin, EE

Araujo, N

Pugh, MD

Cristiano, MLS

Stocks, PA

Bachi, MD

机构：

[1] Univ Liverpool, Dept Chem, Liverpool L69 3BX, Merseyside, England

[2] Univ Liverpool, Liverpool Sch Trop Med, Dept Organ Chem, Liverpool L3 5QA, Merseyside, England

[3] Weizmann Inst Sci, IL-76100 Rehovot, Israel

[4] Univ Algarve, FCT, P-8000 Faro, Portugal

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 11期

基金：

英国生物技术与生命科学研究理事会; 英国工程与自然科学研究理事会;

关键词：

artemisinin; arteflene; endoperoxide; malaria; mechanism of action;

D O I：

10.1016/j.bmcl.2006.02.059

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A Diels-Alder/thiol-olefin co-oxygenation approach to the synthesis of novel bicyclic endoperoxides 17a-22b is reported. Some of these endoperoxides (e.g., 17b, 19b, 22a and 22b) have potent nanomolar in vitro antimalarial activity equivalent to that of the synthetic antimalarial agent arteflene. Iron(II)-mediated degradation of sulfone-endoperoxide 19b and spin-trapping with TEMPO provide a spin-trapped adduct 25 indicative of the formation of a secondary carbon centered radical species 24. Reactive C-radical intermediates of this type may be involved in the expression of the antimalarial effect of these bicyclic endoperoxides. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：2991 / 2995

页数：5

共 24 条

[1] Synthesis and in vitro antimalarial activity of sulfone endoperoxides [J].