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Synthetic studies on marine polycyclic ethers and their derivatives

海洋多环醚及其衍生物的合成研究

基本信息

批准号：
15390009
负责人：
NAKATA Tadashi
金额：
$ 9.66万
依托单位：
Tokyo University of Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

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

自1981年首次分离出短链藻毒素-B以来，许多海洋多环醚（例如短链藻毒素、甘比尔醇和麦芽毒素）因其具有合成挑战性的复杂结构和强大的生物活性而吸引了众多合成有机化学家的关注。这些天然产物的结构特征是反式稠合的多环醚环体系。因此，人们广泛研究了各种构建环醚环系的方法，并对海洋多环醚的全合成进行了研究。在本研究项目中，我们开发了多环醚的构建新方法，完成了海洋多环醚的全合成和部分合成。开发了几种高效的反式稠合多环醚的构建方法； (1)基于碘酯与SmI_2-NiI_2分子内Barbier反应和路易斯酸促进半缩醛粘液还原的收敛方法。 (2) 另一种聚合方法，以碘酯与叔丁基锂或正丁基锂的分子内巴比耶反应为关键步骤。 (3)基于偶姻缩合的环醚合成新方法。 (4)基于SmI_2诱导(E)-和(Z)-β-烷氧基乙烯基砜与醛的还原环化立体选择性合成2,6-syn-2,3-反式和2,6-syn-2,3-顺式四氢吡喃。对海洋多环醚的全合成和部分合成进行了广泛研究。基于双向合成策略，利用SmI_2诱导的β-烷氧基丙烯酸酯还原环化，完成了短尾毒素-B的全合成。分别基于双向策略、收敛策略和环氧醇内环化合成了虾毒素的ABCDE环、FGHIJ环和K环。以SmI_2诱导的环氧醇还原环化、内环化为基础，完成了麦芽毒素WXYZA'环的合成。基于SmI_2诱导的β-烷氧基丙烯酸酯和β-烷氧基乙烯基砜的还原环化反应，合成了裸菌素的FGH环和KLMN环。基于碘酯与SmI_2-NiI_2的分子内Barbier反应，完成了甘比尔醇ABC环和EFG环的偶联，并合成了DEFG环。较少的