The syntheses of kulkenon and sulfangolide

库克酮和磺胺内酯的合成

• 批准号: 233345793
• 负责人: Professor Dr. Markus Kalesse
• 金额: --
• 依托单位: Institut für Organische Chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/233345793?language=en
• 关键词: syntheses; kulkenon; sulfangolide

Sulfangolide and kulkenon are new secondary metabolites from myxobacteria. The sulfangolides are special since they were the first secondary metabolites from myxobacteria that exhibit a sulfate ester. Its structure was analyzed with the aid of NMR experiments and computer aided calculations. This structure elucidation set the background for our synthesis of both compounds. During the synthesis of kulkenon we realized that this structure elucidation was not describing the correct configuration at two stereocentres. Due to our work on kulkenon we could not only complete the first total synthesis of this natural product but also determine its correct configuration. We expect that this refinement will also apply to the sulfangolides. The synthesis of sulfangolide is to provide synthetic access to this unusual natural product and to provide an example of our vinylogous Mukaiyama aldol reaction and to show how this might shorten the number of steps during the synthesis of a complex natural product. Before, these fragments were constructed by either standard aldol and olefination protocols or by a classical vinylogous aldol reaction followed by a Mitsunobu inversion. Another unusual transformation is the intramolecular Heck reaction as macrocyclization protocol. Due to the fact that we had to re-investigate the configuration of kulkenon and restart its synthesis we used more time for this part of the project than initially planned. In addition, we encountered significant problems when performing the aldol connection between C16 and C17. The project is designed to complete the synthesis of sulfangolide and to confirm its configuration. As an additional methodological aspect we plan to investigate the aforementioned aldol reaction in detail since there are only few examples and some of these results seem to be contradictory.

Sulfangelate和kulkenon是粘细菌中新的次级代谢产物。硫节苷脂是特殊的，因为它们是粘细菌中第一个表现出硫酸酯的次级代谢产物。借助核磁共振实验和计算机辅助计算分析了它的结构。这一结构解析为我们合成这两种化合物奠定了基础。在Kulkenon的合成过程中，我们意识到这种结构解析并没有描述两个立构中心的正确构型。由于我们对kulkenon的工作，我们不仅可以完成这种天然产物的第一个全合成，而且还确定了它的正确构型。我们预计，这种改进也将适用于磺胺内酯。磺胺甲恶唑的合成是为了提供合成这种不寻常的天然产物的途径，并提供我们的乙烯基化合物Mukaiyama羟醛缩合反应的一个例子，并显示这如何缩短合成复杂天然产物的步骤。以前，这些片段是通过标准的羟醛和烯化方案或通过经典的乙烯基羟醛反应，然后通过Mitsunobu转化来构建的。另一个不寻常的转变是作为大环化协议的分子内Heck反应。由于我们不得不重新研究kulkenon的结构并重新开始合成，我们在这部分项目上花费的时间比最初计划的要多。此外，我们在进行C16和C17之间的羟醛连接时遇到了重大问题。本项目旨在完成磺胺甲恶唑的合成并确定其构型。作为一个额外的方法学方面，我们计划详细研究上述羟醛反应，因为只有很少的例子，其中一些结果似乎是矛盾的。