Development of Efficient Methods for the Synthesis of Polycyclic Ethers

自首次分离出由赤潮生物短梭子藻（Gymnodinium breve）产生的神经毒素brevetoxin B以来，已报道了许多这种类型的海洋多环醚。这些天然产物最显著的结构特征是跨熔多环醚环体系。其独特的合成结构和强大的生物活性引起了众多有机合成化学家的关注。在本项目中，我们开发了一种基于smi_2诱导的还原性分子内环化的非常简单和高效的迭代合成多四氢吡喃环体系的策略。该方法也适用于合成多环醚环体系，包括氧烷和角甲基。在此基础上，提出了一种双向合成多环醚的方法。基于两个四氢吡喃的乙酰基-三氟酸偶联，炔基氧化为A -二酮，双环化为6,6,6,6元四环双缩醛，并用Et_3SiH-TMSOTf对双缩醛进行立体选择性还原，建立了一种高效的聚类策略，构建了6-6-6-6元四环醚环体系。综上所述，我们已经开发出一种非常简单和有效的方法来构建跨熔多环醚环体系。该方法可广泛应用于天然多环醚的高效合成

Since the first isolation of brevetoxin B, a neurotoxin produced by the red tide organism Gymnodinium breve, many marine polycyclic ethers of this type have been reported. The most characteristic structural feature of these natural products is trans-fused polycyclic ether ring system. The synthetically challenging unique structures and their potent biological activities have attracted the attention of numerous synthetic organic chemists.In this project, we have developed an extremely facile and highly efficient strategy for the iterative synthesis of a trans-fused polytetrahydropyran ring system based on the SmI_2-induced reductive intramolecular cyclization. This method is also effective for the synthesis of polycyclic ether ring systems including oxepane and also an angular methyl group. Based on the present SmI_2-induced cyclization, a strategy for two directional synthesis of polycyclic ether was developed.A very efficient convergent strategy for the construction of the trans-fused 6-6-6-6-membered tetracyclic ether ring system was developed based on the acetylide-triflate coupling of two tetrahydropyrans, oxidation of the alkyne group to an a-diketone, double cyclization to 6,6,6,6-membered tetracyclic diacetal, and stereoselective reduction of the diacetal with Et_3SiH-TMSOTf.In conclusion, we have developed very simple and efficient strategies for the construction of trans-fused polycyclic cyclic ether ring system. This strategy would be widely applicable to efficient syntheses of natural polycyclic ethers