Atom economic rhodium-catalyzed synthesis of lactones as key step for the construction of natural macrolactones

原子经济铑催化内酯合成是构建天然大内酯的关键步骤

• 批准号: 315326950
• 负责人: Professor Dr. Bernhard Breit
• 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: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/315326950?language=en
• 关键词: Atom; economic; rhodium; catalyzed; synthesis

Makrolactones as well as Makrodiolides represent important classes of natural products with a wide range of biological activities. The development of efficient catalytic methodology for their intrinsic waste-free i.e. atom economic synthesis under direct construction of the lactone function is basically unknown. Hence, the goal of this project is the development of a generally applicable atom economic and stereoselective macrolactonization applying an atom economic rhodium-catalyzed intramolecular addition of carboxylic acids to terminal alkynes and allenes. Subsequent to establishing this method its utility shall be probed in the context of the total synthesis of two biologically and medicinally interesesting natural product families, the epothilones B, D, and F as respresentatives for the class of macrolactones, and Samroiytmycin A as a representative for the class of macrodiolides. The envisioned synthesis strategy would enable a flexible late stage functionalization of the macrolactone and macrodiolide cores thus enabling a simple access to potentially biologically active compounds. The so-obtained natural product derivatives shall be tested with regard to their biological activities together with the Helmholtz-Institute for Pharmaceutical Research in Saarbrücken.

马克罗内酯和马克罗内酯是一类重要的天然产物，具有广泛的生物活性。开发高效的催化方法来实现其内在的无废物，即直接构建内酯功能下的原子经济合成，基本上是未知的。因此，本项目的目标是开发一种普遍适用的原子经济的和立体选择性的大内酯化反应，应用原子经济的铑催化的羧酸与末端炔烃和烯的分子内加成反应。在建立了该方法之后，应在全合成两个具有生物和药用价值的天然产品家族的背景下探索其实用性，其中，作为大内酯类的代表性的Epothilone B、D和F，以及作为大二内酯类的代表的Samroiytmycin A。设想的合成战略将实现大内酯和大内酯核心的灵活后期官能化，从而能够简单地获得潜在的生物活性化合物。这样获得的天然产物衍生物应与萨尔布吕肯的亥姆霍兹药物研究所一起进行生物活性测试。

项目成果

Concise Total Synthesis of (-)-Vermiculine through a Rhodium-Catalyzed C2 -Symmetric Dimerization Strategy.

• DOI: 10.1002/chem.201900216
• 发表时间: 2019-03
• 期刊: Chemistry
• 作者: Philip Steib;B. Breit