Antimalarial artemisinin analogs. Synthesis via chemoselective C-C bond formation and preliminary biological evaluation

被引：36

作者：

O'Dowd, H

Ploypradith, P

Xie, SJ

Shapiro, TA

Posner, GH ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Arts & Sci, Dept Chem, Baltimore, MD 21218 USA

[2] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

来源：

TETRAHEDRON | 1999年 / 55卷 / 12期

关键词：

chemoselective carbonyl additions; peroxide bond stability; antimalarial; trioxanes; artemisinin;

D O I：

10.1016/S0040-4020(98)01170-3

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The peroxide bond in artemisinin trioxane lactone (1) withstood exposure to lithiothiazole and to lithiobenzothiazole; nucleophilic addition of these powerful organometallic reagents to only the lactone carbonyl group was observed. Likewise, trioxane aldehyde 5 reacted with organolithium, Grignard, and phosphorus ylide nucleophiles exclusively via carbonyl addition. Also, trioxane ketone 7b reacted with phenyllithium via only carbonyl addition. These chemoselective lactone, aldehyde, and ketone carbonyl addition reactions produced a series of new, enantiomerically pure, C-10 non-acetal derivatives of natural trioxane artemisinin having high in vitro antimalarial potencies. (C) 1999 Elsevier Science Ltd. All rights reserved.

引用

页码：3625 / 3636

页数：12

共 35 条

[1] Synthesis and in vivo antimalarial activity of 12 alpha-trifluoromethyl-hydroartemisinin [J].