Total synthesis of 11-membered cytochalasins as new molecular tools

细胞松果酸是一组天然产物的成员，它们以一个共同的骨架为基础进行各种生物学活动。观察到，天然产品可以利用一个共同的主干达到不同的生物目标，这一观察结果也适用于其他天然产品。对这一现象进行系统的去卷积，并确定控制特异性的因素，对于天然产物领域以及药物化学领域都具有重要的价值。为了确定生物目标和描述导致解决这些目标的因素，综合获取是必不可少的。由11名成员组成的细胞松弛素组中的6名成员将通过该项目获得合成通道，并为生物研究提供通道。这些合成提出了一种后期氨基侧链的掺入，从而使各种衍生物的快速合成成为可能。除了蛋白质生成氨基酸的侧链，荧光芳香族化合物也可以被掺入。这些化合物可用于靶标识别和细胞定位。这些合成使用了两个顺式或反式取代的侧链，这两个侧链是本课题组建立的。对于宏观环化，将使用Ramberg-Bäck lund反应，从而建立一种史无前例的细胞松弛素合成策略，这将提高环化效率。

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.