Total synthesis of 11-membered cytochalasins as new molecular tools

作为新分子工具的11元细胞松弛素的全合成

• 批准号: 455074671
• 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 Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/455074671?language=en
• 关键词: Total; synthesis; 11; membered; cytochalasins

Cytochalasine are members of a group of natural products, which effect a variety of biological activities based on one common backbone. The observation that natural products can address different biological targets using one common backbone can also be made for other natural products. A systematical deconvolution of this phenomenon and the identification of the factors controlling specificity can be of important value for the field of natural products as well as for medicinal chemistry. For the identification of biological targets and the description of factors that result in addressing these targets synthetic access is essential. For six members of the group of 11-membered Cytochalasins synthetic access will be secured with this project and provided for biological investigations. The syntheses propose a late-stage incorporation of amino side chains and thus enable the rapid synthesis of a variety of derivatives. Besides the incorporation of side chains of proteinogenic amino acids, fluorescente aromatic compounds can be incorporated as well. These compounds can be used for target identification and cell localization. The syntheses use two cis or trans-substituted side chains which synthesis was established in our group. For the macro cyclization a Ramberg-Bäcklund reaction will be used and thus establish an unprecedented strategy for cytochalasin synthesis which will enhance cyclisation efficiency.

细胞松弛素是一类具有多种生物活性的天然产物。天然产物可以使用一个共同的骨架针对不同的生物靶标的观察也可以针对其他天然产物进行。系统地解卷积这一现象，并确定控制特异性的因素，可以为天然产物领域以及药物化学的重要价值。为了确定生物目标和说明导致处理这些目标的因素，综合准入是必不可少的。对于11元细胞松弛素合成组的六个成员，将通过该项目获得并提供生物学研究。该合成提出了氨基侧链的后期掺入，从而能够快速合成各种衍生物。除了蛋白质氨基酸的侧链的掺入之外，还可以掺入荧光芳香族化合物。这些化合物可用于靶标识别和细胞定位。该合成使用两个顺式或反式取代的侧链，其合成在我们组中建立。对于大环化，将使用Ramberg-Bäcklund反应，从而建立一种前所未有的细胞松弛素合成策略，这将提高环化效率。