Organic Synthesis Using Oxiranyl Anions

氧杂环丙烷基阴离子是亲核的，它们与多种亲电试剂的反应为将氧杂环氧基直接引入有机分子提供了一种新的方法。本课题研究了氧杂环氧基阴离子的生成、反应及其在天然产物合成中的应用。氧杂环氧基阴离子的烷基化磺基稳定的氧杂环氧基阴离子，通过相应的环氧砜与n-BuLi在-100℃的四氢呋喃中去质子化得到，与三氟甲磺酸酯(三氟酸盐)反应，以高产率得到偶联产物。6-内环合成聚四氢吡喃提出了一种合成反式聚四氢吡喃的新方法。该方法包括两个关键反应：(I)磺酰基稳定的氧杂环氧基阴离子与三氟化物的烷基化反应，(Ii)在吸电子磺酰基团的辅助下，酸促进生成的羟基环氧砜的6-内环化反应。甲基取代六元环醚的合成。基于甲基取代羟基环氧磺酸的6-内环化反应，开发了一种合成环氧邻位甲基四氢吡喃的一般方法。半短杆菌毒素B的合成半短杆菌毒素B是从赤潮生物短裸甲藻培养细胞中分离得到的一种多环醚海洋毒素，具有独特的6，6，7，7-四环醚环体系。采用氧杂环丙烷基阴离子策略完成了半短杆菌毒素B的正式全合成。

Oxiranyl anions are nucleophilic and their reaction with a variety of electrophiles provides a new methodology for introducing an oxiranyl group directly into organic molecules. The generation and reaction of oxiranyl anions and their applications to natural product synthesis were carried out in this project.1. Alkylation of oxiranyl anionsSulfonyl-stabilized oxiranyl anions, gerenated by deprotonation of the corresponding epoxy sulfones with n-BuLi in THF at -100℃, reacted with trifluoromethanesulfonate esters (triflate) to give the coupled products in high yield.2. Synthesis of polytetrahydropyrans by 6-endo cyclizationThe new method for the synthesis of trans-fused polytetrahydropyrans was developed. The approach involves two key reactions : (i) alkylation of a sulfonyl-stabilized oxiranyl anion with a triflate, (ii) acid-promoted 6-endo cyclization of the resulting hydroxy epoxy sulfone assisted by the electron-withdrawing sulfonyl group.3. Synthesis of methyl-substituted 6 membered cyclic ethers.A general procedure for the synthesis of tetrahydropyrans having methyl groups adjacent to the ring oxygen was developed based on the 6-endo cyclization of methyl-substituted hydroxy epoxy sulfones.4. Synthesis of Hemibrevetoxin BHemibrevetoxin B is one of polycyclic ether marine toxins isolated from the cultured cells of the red tide organism Gymnodinium breve and has the unique 6,6,7,7-tetracyclic ether ring system. The formal total synthesis of hemibrevetoxin B was accomplished by using oxiranyl anion strategy.