Core C: Organic Synthesis Core - Total Synthesis of Specialized Pro-Resolving Lipid Mediators

7.项目摘要/摘要 有机合成核心(核心C)将为该研究计划提供必要的化学支持 通过合成和表征新型专门化前拆分介体(SPM)及其性能 硫代偶联物(SPM-SC)。核心将负责一组新型SPM的总合成 和相关的SPM探针，包括：溶剂素、树脂、硫化物结合物和其他相关分子 这将在这个计划下进行研究。 核心C将开发和利用有效的立体控制合成途径，用于全合成 立体化学纯形式的靶向SPM，并建立合适的方法对其进行详细纯化 以及使用光谱技术进行结构验证。核心C还将准备所需的数量(增加 至mg级)，并将致力于设计和合成将 使他们能够进行生物调查。C芯还将制备同位素取代的SPM衍生物，以 作为SPM探针与核心B和项目1、2和3合作进行脂肪组分析，而其他 SPM探针将作为用于机械研究的放射性标记衍生物的前体。最后，核心C 将与项目1、2和3以及核心A-B就涉及新生物的拟议研究进行合作 SPM的作用和细胞机制。 总体而言，这些合作调查将有助于阐明SPM尚未探索的关键功能，并将 帮助验证它们在消退炎症和组织再生方面的功能作用(S)。

7. PROJECT SUMMARY / ABSTRACT The Organic Synthesis Core (Core C) will provide essential chemistry support for this research program through the synthesis and characterization of novel specialized pro-resolving mediators (SPM) and their sulfido-conjugates (SPM-SC). The Core will be responsible for the total synthesis of a panel of novel SPMs and related SPM probes, including: resolvins, maresins, sulfido-conjugates, and other related molecules that will be studied under this program. Core C will develop and utilize effective stereocontrolled synthetic pathways for the total synthesis of the targeted SPM in stereochemically pure form, and establish suitable methods for their detailed purification and structural verification using spectroscopic techniques. Core C will also prepare needed quantities (up to mg scale) of selected SPM, and will pursue the design and synthesis of selected derivatives that will enable their biological investigation. Core C will also prepare isotopically substituted SPM derivatives to serve as SPM probes for lipidomic profiling in collaboration with Core B and Project 1, 2, and 3, while other SPM probes will serve as precursors of radiolabelled derivatives for mechanistic studies. Finally, Core C will collaborate with Projects 1, 2 and 3 and Cores A-B on the proposed studies involving novel biological actions and cellular mechanisms of SPMs. Overall, these collaborative investigations will help elucidate key unexplored functions of SPMs, and will help validate their functional role(s) in the resolution of inflammation and tissue regeneration.