Simplified analogs of the antimalarial artemisinin: synthesis of 6,9-desmethylartemisinin
Simplified analogs of the antimalarial artemisinin: synthesis of 6,9-desmethylartemisinin
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抗疟青蒿素的简化类似物：6,9-去甲基青蒿素的合成
DOI：
10.1021/jo00269a009
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发表时间：
1989
影响因子：
3.6
通讯作者：
W. Chong
中科院分区：
文献类型：
--
作者：
M. Avery;C. Jennings;W. Chong
(±)-6, 9-Desmethylartemisinin (8) was prepared from pyrrolidinocyclohexene and cts-1, 4-dichloro-2-butene in eight steps. The intermediacy of bicyclic 2 led to a stereocontrolled route to pivotal syn-substituted cyclohexane 5. Hydrolysate keto acid vinylsilane 7 underwent abnormal reaction with ozone and subsequent acid-catalyzed cyclization to the title compound.The natural product (+)-artemisinin has exhibited an-timalarial activity against chloroquine-resistant P. falci-parum. 1 The unique peroxide-containing sesquiterpene structure is depicted here by 1. Despite its use in ancient Chinese medicine and, more recently, structural elucidation in 1980, many details of the molecular basis for antima-larial activity by artemisinin remain unknown. The emergence of quinine-resistant malaria in tropical regions and the challenge of such a target structure for total synthesis have focused attention upon artemisinin from many laboratories, 2 including our own. We have recently re-ported the total synthesis of (+)-artemisinin3 and are presently engaged in a program for the synthesis of novel analogues4 that are intended to identify a responsible pharmacophore for the design of improved antimalarials.
