Total Synthesis of (±)-Cylindrospermopsin
Total Synthesis of (±)-Cylindrospermopsin
复制标题
(±)-Cylindrospermopsin 的全合成
DOI：
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发表时间：
2000
期刊：
影响因子：
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通讯作者：
B. Snider
中科院分区：
文献类型：
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作者：
C. Xie;and Maria T. C. Runnegar;B. Snider
以4-甲氧基-3-甲基吡啶（12）为起始原料，经20步反应首次全合成了新的肝毒素（±）-柱孢霉酚（1），总收率3.5%。取代的哌啶A环19通过四步顺序立体特异性地产生，使用三甲基甲硅烷基乙炔基溴化镁加成到12上得到16，并立体特异性地加成乙烯基铜酸酯到16上形成17。二胺26与溴化氰反应生成环胍C环27。合成中的关键步骤是酮31的溴化，然后氢化以释放游离胍，游离胍经历分子内SN 2反应以形成32的四氢嘧啶环B。进一步氢化还原酮，得到42%的32，其含有完全官能化的三环系统和柱精子蛋白酶的保护的羟甲基尿嘧啶侧链。嘧啶在浓盐酸中水解，选择性单硫酸化，完成了柱孢菌素的合成。
The first total synthesis of the novel hepatotoxin (±)-cylindrospermopson (1) has been accomplished in 20 steps from 4-methoxy-3-methylpyridine (12) in 3.5% overall yield. The substituted piperidine A ring 19 was generated stereospecifically by a four-step sequence using the addition of trimethylsilylethynylmagnesium bromide to 12 to give 16 and stereospecific addition of vinylcuprate to 16 to form 17. The reaction of diamine 26 with cyanogen bromide produced the cyclic guanidine C ring of 27. The key step in the synthesis was bromination of ketone 31, followed by hydrogenation to liberate the free guanidine, which underwent an intramolecular SN2 reaction to form the tetrahydropyrimidine ring B of 32. Further hydrogenation reduced the ketone to yield 42% of 32 containing the fully functionalized tricyclic system and protected hydroxymethyluracil side chain of cylindrospermopsin. Hydrolysis of the pyrimidine in concentrated hydrochloric acid and selective monosulfation completed the synthesis of cylindrosp...
谷胱甘肽在培养大鼠肝细胞中新型蓝藻生物碱圆柱精蛋白的毒性中的作用。
影响因子：
3.1
作者：
Runnegar,MT;Kong,SM;Zhong,YZ;Ge,JL;Lu,SC
通讯作者：
Lu,SC