Total Synthesis of Ryanodol
Total Synthesis of Ryanodol
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DOI：
10.1021/ja502770n
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发表时间：
2014-04-23
影响因子：
15
通讯作者：
Inoue, Masayuki
中科院分区：
文献类型：
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作者：
Nagatomo, Masanori;Koshimizu, Masaki;Inoue, Masayuki
Ryanodol(1)以1h -吡咯-2-羧酸酯衍生物ryanodine的形式存在于自然界中，它是钙释放通道的有效调节剂。由8个氧基、3个甲基和1个异丙基组成了5环abcde - 1体系。所有八个四取代立体中心都集中在10碳ABDE框架内。这个异常复杂的分子的合成从简单的c -2对称三环到22步就完成了。合成路线是基于七个立体中心的安装和在高度拥挤的多环格式中形成四个C-C键。这里开发的新颖灵活的策略将能够生成具有不同功能特性的钙释放通道的化学衍生物。
Ryanodol (1) exists in nature in the form of the 1H-pyrrole-2-carboxylate ester derivative known as ryanodine, which is a potent modulator of the calcium release channel. The pentacyclic ABCDE-ring system of 1 is fabricated with eight oxy groups, three methyl groups, and one isopropyl group. All the eight tetrasubstituted stereocenters are concentrated within the 10-carbon ABDE framework. The total synthesis of this exceptionally complex molecule was achieved in 22 steps from the simple C-2-symmetric tricycle 8. The synthetic route is based on installation of the seven stereogenic centers and formation of the four C-C bonds within the highly congested multicyclic format. The novel and flexible strategy developed here will enable the generation of chemical derivatives with different functional properties toward calcium release channels.