One‐Step Synthesis of the 1‐Azaspiro[5.5]undecane Skeleton Characteristic of Histrionicotoxin Alkaloids from Linear Substrates via Hg(OTf)<sub>2</sub>‐Catalyzed Cycloisomerization
One‐Step Synthesis of the 1‐Azaspiro[5.5]undecane Skeleton Characteristic of Histrionicotoxin Alkaloids from Linear Substrates via Hg(OTf)<sub>2</sub>‐Catalyzed Cycloisomerization
复制标题
Hg(OTf)<sub>2</sub>催化环异构化从线性底物一步合成1-氮杂螺[5.5]十一烷骨架特征的曲霉毒素生物碱
DOI：
10.1002/asia.202100383
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
and Yoshiki Morimoto
中科院分区：
文献类型：
--
作者：
Kunihiro Matsumura;Keisuke Nishikawa;Hiroaki Yoshida;Toshiki Niwa;Yuichiro Fushii;Matsumi Doe;and Yoshiki Morimoto
从毒箭蛙中分离出的Histrionicotoxin （HTX）生物碱具有HTX家族常见的1 - azspiro[5.5]十一烷骨架。HTXs独特的分子结构和作为潜在靶标药物的兴趣促使合成化学家们迄今为止一直在促进其全合成。然而，所有获得HTXs的1 -氮杂环[5.5]十一烷框架的合成策略都需要从线性起始材料开始，通过逐步构建六元碳环或氮杂环来采取多步骤的方法。在此，我们报道了利用三酸汞（Hg(OTf)2）催化的环异构化反应，从含有anN -甲氧基羰基的线性氨基基底物直接一步构建1 -氮杂灵[5.5]十一烷骨架。通过azaspirocycle分别合成HTX‐235A和HTX‐283A，证明了这种新方法的实用性。
Histrionicotoxin (HTX) alkaloids isolated from the poison arrow frogs possess a unique structure characterized by a 1‐azaspiro[5.5]undecane skeleton common to the HTX family. The unique molecular architecture of HTXs and the interest as potential target drugs have prompted synthetic chemists to promote the total synthesis so far. However, all of the synthetic strategies to access the 1‐azaspiro[5.5]undecane framework of HTXs take a multistep approach from linear starting materials due to stepwise construction of either six‐membered carbo‐ or azacycle. Herein, we report the direct one‐step construction of the 1‐azaspiro[5.5]undecane skeleton from linear amino ynone substrates bearing anN‐methoxycarbonyl group utilizing our mercuric triflate (Hg(OTf)2)‐catalyzed cycloisomerization reaction. The utility of this novel methodology was demonstrated by the total and formal syntheses of HTX‐235A and HTX‐283A, respectively, from the azaspirocycle.