Synthetic studies on marine polycyclic ethers and their derivatives

自1981年首次分离出短草毒素b以来，许多海洋多环醚，如短草毒素、甘比醇和maitotoxin，由于其复杂的合成结构和强大的生物活性，引起了许多合成有机化学家的关注。这些天然产物的结构特点是跨熔多环醚环体系。因此，人们对各种环醚环体系的构建方法进行了广泛的研究，并对海洋多环醚的全合成进行了研究。本课题开发了构建多环醚的新方法，完成了海洋多环醚的全合成和部分合成。提出了几种高效的聚环醚合成方法；(1)基于碘酯与SmI_2-NiI_2分子内Barbier反应和Lewis酸促进半缩醛黏液还原的会聚方法。(2)以t-BuLi或n-BuLi为关键步骤，基于碘酯分子内Barbier反应的更收敛的替代方法。(3)一种基于丙环醛缩合合成环醚的新方法。(4)基于smi_2诱导(E)和(Z)-β-烷氧乙烯基砜与醛还原环化合成2,6-syn-2,3-反式和2,6-syn-2,3-顺式四氢吡喃的立体选择性方法。广泛研究了海洋多环醚的全合成和部分合成。采用smi_2诱导β-烷氧丙烯酸酯还原环化的双向合成策略，完成了brevetoxin-B的全合成。利用双向策略、聚合策略和环氧醇内环分别合成了叶毒素的abcde环、fghij环和k环。在smi_2诱导环氧醇还原环化、内环化的基础上，合成了maitotoxin的WXYZA'-环。以β-烷氧基丙烯酸酯和β-烷氧基乙烯基砜为原料，通过smi_2诱导的还原环反应合成了gymnocin的fgh -环和klmn -环。通过碘酯与SmI_2-NiI_2的分子内Barbier反应，实现了甘比罗的ab -和efg环的偶联，并合成了defg环。少

Since the first isolation of brevetoxin-B in 1981, many marine polycyclic ethers, exemplified by brevetoxins, gambierol, and maitotoxin, have attracted the attention of numerous synthetic organic chemists due to their synthetically challenging complex structures and their potent bioactivities. The structural feature of these natural products is a trans-fused polycyclic ether ring system. Thus, various methods for construction of cyclic ether ring system have been extensively studied and the total synthesis of marine polycyclic ethers have been studied. In this research project, we have developed new methods for the construction of polycyclic ethers and accomplished total and partial synthesis marine polycyclic ethers.Several efficient methods for the construction of trans-fused polycyclic ethers were developed ; (1) a convergent method based on an intramolecular Barbier reaction of iodo ester with SmI_2-NiI_2 and Lewis acid-promoted slime reduction of hemiacetal. (2) an alternative con … More vergent method based on an intramolecular Barbier reaction of iodo ester with t-BuLi or n-BuLi as a key step. (3) a new method for synthesis of cyclic ether based on acyloin condensation. (4) stereoselective method for the synthesis of 2,6-syn-2,3-trans-and 2,6-syn-2,3-cis-tetrahydropyrans based on SmI_2-induced reductive cyclization of (E)-and (Z)-β-alkoxyvinylsulfones with aldehyde.Total and partial syntheses of marine polycyclic ethers were extensively investigated. Total synthesis of brevetoxin-B was accomplished based on two-directional synthetic strategy using SmI_2-induced reductive cyclization of β-alkoxyacrylate. The ABCDE-ring, FGHIJ-ring, and K-ring of yessotoxin were synthesized based on two-directional strategy, convergent strategy, and endo-cyclization of epoxy alcohol, respectively. The synthesis of WXYZA'-ring of maitotoxin was accomplished based on SmI_2-induced reductive cyclization, endo-cyclization of epoxy alcohol. The synthesis of FGH-ring and KLMN-ring of gymnocin was accomplished based on SmI_2-induced reductive cyclizations using β-alkoxyacrylate and β-alkoxyvinylsulfone. The coupling of ABC-and EFG-rings of gambierol was accomplished based on an intramolecular Barbier reaction of iodo ester with SmI_2-NiI_2, and DEFG-ring was also synthesized. Less