Synthetic Studies on Endistonins, Which Potent Anti-virel Activity.

本研究的目的是建立一条高效、实用的合成路线来合成具有抗病毒和抗肿瘤活性的eudistomins。在对合成路线进行了基本探索之后，我们彻底研究了利用我们的吲哚合成通过邻烯基硫代苯胺的自由基环化的策略。通过β-内酰胺稠合体系成功地立体选择性地合成了7元氧硫氮杂环。虽然可以得到所需的吲哚形成前体，但尽管对反应条件进行了广泛的研究，预期的吲哚形成反应根本没有发生。然而，在研究过程中，我们开发了一种新的伯胺转化为N-烷基羟胺的方法，然后我们将注意力转向开发一种新的通过巯基的分子内缓和形成oxathiazepin的方法。最后，我们实现了具有高度非对映选择性的（-）-eudistomin C的全合成。 ...更多信息 二氯乙酸催化的d-Spenglar反应，以及一种新的生成氧硫氮杂卓的方法。利用分子内Heck反应通过Macor方法制备所需的吲哚片段。在通过Mitsunobu反应转化为用甲硫基甲基（MTM）保护的羟胺衍生物后，使该化合物与加纳醛进行Picted-Spengler反应条件。在二氯乙酸的存在下，高选择性地得到了所需的非对映体。通过在碱存在下用磺酰氯和硫代乙酸处理MTM保护的化合物使其转化为硫代乙酸酯，开始关键的氧硫硫氮杂卓的形成。官能团操作后，所得的带有甲磺酸酯和硫代乙酸酯官能团的环化前体在甲醇中用碳酸钾处理，以高产率提供氧硫氮杂卓环。最后用溴化三硼脱Boc和甲氧基保护，完成了（-）-eudistomin C的全合成。少

The aim of this research is to establish an efficient and practical synthetic route to eudistomins, which have proved to possess potent anti-viral and anti-tumor activity. After fundamental explorations of the synthetic route, we thoroughly investigated a strategy utilizing our indole synthesis by radical cyclization of o-alkenylthioanilides. The stereoselective formation of the 7-membered oxathioazepin ring was successfully achieved via β-lactam fused system. Although the desired indole formation precursor could be obtained, the expected indole formation reaction did not take place at all in spite of extensive investigation on the reaction conditions. In the course of investigation, however, we have developed a novel transformation of primary amines to N-alkylhydroxylamines.We then turned our attention to develop a novel formation of oxathiazepin by intramolecular alleviation of thiol. Finally, we achieved a total synthesis of (-)-eudistomin C featuring highly diastereoselective Picte … More d-Spenglar reaction catalyzed by dichloroacetic acid, and a novel protocol for the formation of oxathiazepin. The requisite indole segment was prepared by Macor's procedure exploiting intramolecular Heck reaction. After conversion to hydroxylamine derivative protectin with methyl thiomethyl (MTM) group by Mitsunobu reaction, the compound was subjected to Picted-Spengler reaction conditions with the Garner's aldehyde. In the presence of dichloroacetic acid, the desired diastereomer was obtained in high selectivity. The crucial oxathiazepin formation was started by conversion of MTM protected compound to thioacetate by treatment with sulfuly1 chloride and thioacetice acid in the presence of base After functional group manipulation, the obtained cyclization precursor bearing mesylate and thioacete functionalities was treated with potassium carbonate in methanol to furnish the oxathiazepin ring in high yield. Finally, total synthesis of (-)-eudistomin C was completed by deprotection of Boc and methoxu group with BBr_3. Less