Collaborations in Chemistry: Putative Intermediates in the Biosynthesis of Tedanolide

该项目将通过多学科合作研究聚酮生物合成和进化的基本方面。Richard Taylor小组（圣母大学）和Markus Kalesse教授小组（汉诺威莱布尼茨大学）之间的协同合成努力，针对的是海洋聚酮tedanolide生物合成中的假定中间体。假定的生物合成中间体，如目前提议的目标，是化学多样性的一个有价值的新来源，具有发现新的生物目标和潜在的新作用方式的潜力。此外，异泰德内酯的合成将为探索1,5-酰基迁移的可行性提供一个独特的机会，这是提出的泰德内酯生物来源途径的关键步骤。生物学分析将在亥姆霍兹疾病感染中心（HZI布伦瑞克）的Florenz Sasse博士的指导下进行。通过这个奖项，有机和大分子化学项目和国际科学与工程办公室支持圣母大学化学与生物化学系Richard Taylor教授的研究。该奖项与德国研究机构（DFG）为汉诺威莱布尼茨大学Markus Kalesse博士和Helmholtzzentrum fr Infektionsforschung GmbH的Florenz Sasse博士资助的合作奖相协调。他们的研究项目包括开发合成和生物合成方法，以识别受天然产物及其生产生物体进化启发的新的生物活性化学实体。成功地准备这些高度复杂的目标，如在这个项目中提出的，将通过开发新的合成方法和策略，同时为研究生和本科生同事提供一个培训平台。此外，对所制备衍生物的补充生物学研究将探索聚酮合成酶后修饰在聚酮生物合成中的进化作用，从而提供具有基础意义的新信息。

This project will investigate fundamental aspects of polyketide biosynthesis and evolution through a multidisciplinary collaboration. A synergistic synthetic effort, between the Richard Taylor group (University of Notre Dame) and the group of Professor Markus Kalesse (Leibniz Universitat Hannover), is directed at the putative intermediates in the biosynthesis of the marine polyketide, tedanolide. Putative biosynthetic intermediates, such as the targets of the current proposal, are a valuable new source of chemical diversity with the potential for discovery of novel biological targets and potentially new modes of action. In addition, the synthesis of iso-tedanolide will provide a unique opportunity to explore the feasibility of a 1,5-acyl migration, a key step in a proposed biogenic pathway to the tedanolides. Biological analyses will be carried out under the direction of Dr. Florenz Sasse at the Helmholtz Zentrum fuer Infektionsforschung (HZI Braunschweig). With this award, the Organic and Macromolecular Chemistry Program and the Office of International Science and Engineering are supporting the research of Professor Richard Taylor of the Department of Chemistry & Biochemistry at the University of Notre Dame. This award coordinates with a collaborative award funded by Deutsche Forschungsgemeinschaft (DFG) for Dr. Markus Kalesse, Leibniz Universitat Hannover and Dr. Florenz Sasse, Helmholtzzentrum für Infektionsforschung GmbH. Their research program involves the development of synthetic and biosynthetic methods for identification of new biologically active chemical entities inspired by the evolution of natural products and their producing organism. Successful preparation of these highly complex targets such as those proposed within this project will be enabled by the development of novel synthetic methods and strategies while providing a training platform for graduate and undergraduate student coworkers. Moreover, complementary biological studies of the prepared derivatives will probe the evolutionary role of post-polyketide synthase modifications in polyketide biosynthesis thus provide new information of fundamental significance.