Synthesis of anatoxin-a
Synthesis of anatoxin-a
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Anatoxin-a的合成
DOI：
10.1021/jo00363a015
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发表时间：
1986
影响因子：
3.6
通讯作者：
Susanna Y. Lee
中科院分区：
文献类型：
--
作者：
J. R. Wiseman;Susanna Y. Lee
本文描述了一种从水藻中提取的生物碱毒素(i)-anatoxin-a的合成方法。9-甲基-9-氮杂环的溴化[3.3]。nonan-l-ol （3b）提供了关键中间体9-甲基-9-氮杂环[4.2]。[1] nonan-2-one(6)。6与膦酸二乙基（l-氰乙基）反应得到2-（l-氰-l-乙基）-9-甲基-9-氮杂二环[4.2]。1]壬烷(8)。8的氧化，随后的还原和水解，得到n-甲基褐藻毒素- 0 (lb)，它已经转化为褐藻毒素-a。Anatoxin-a(1)是从丝状淡水蓝藻Anabaena flos-aquae中分离出来的一种强效生物碱毒素。这种毒素，也被称为“快速死亡因子”（VFDF, lb），在美国中西部和加拿大的淡水湖中，家畜、水禽和其他野生动物在摄入有毒藻类后死亡。(+)-anatoxin-a的结构和绝对构型已被确定为（lR, 6/?）2-acetyl-9-azabicyclo[4.2。[1]非2-烯在1971年通过x射线晶体学得到，与爱德华兹及其同事的光谱研究结果完全一致。la Campbell， Ed-从(2R, 3S)-可卡因立体定向合成(+)-anatoxin-a
A short efficient synthesis of (i)-anatoxin-a, the alkaloidal toxin from Anabaena flos-aquae, is described. Bromination of 9-methyl-9-azabicyclo [3.3. 1] nonan-l-ol (3b) provides the key intermediate 9-methyl-9-azabicyclo [4.2. 1] nonan-2-one (6). Reaction of 6 with diethyl (l-cyanoethyl) phosphonate gives 2-(l-cyano-l-ethylidene)-9-methyl-9-azabicyclo [4.2. 1] nonane (8). Oxygenation of 8, followed by reduction and hydrolysis, gives N-methylanatoxin-o (lb) which has been earlier converted into anatoxin-a.Anatoxin-a (1) is a powerful alkaloidal toxin isolated from the filamentous freshwater cyanophyte Anabaena flos-aquae. u This toxin, also designated as “very fast death factor", VFDF, lb is responsible for the death of livestock, waterfowl, and other wildlife following ingestion of toxic blooms of the alga in freshwater lakes of mid-western United States and Canada. 10 The structure and the absolute configuration of (+)-anatoxin-a has been es-tablished as (lR, 6/?)-2-acetyl-9-azabicyclo [4.2. 1] non-2-ene by X-ray crystallography in 19722a and was in full agree-ment with the spectroscopic studies obtained by Edwards and his co-workers. la The stereospecific synthesis of (+)-anatoxin-a from (2R, 3S)-cocaine by Campbell, Ed-