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

7.项目总结/摘要 有机合成核心（核心C）将为这项研究计划提供必要的化学支持 通过合成和表征新的专门的促消退介质（SPM）及其 硫键-缀合物（SPM-SC）。核心将负责一组新型SPM的全合成 及相关SPM探针，包括：resolvins、maresins、硫键共轭物和其他相关分子 将在这个项目下进行研究。 核心C将开发和利用有效的立体控制合成途径， 靶向SPM的立体化学纯的形式，并建立合适的方法，其详细的纯化 和使用光谱技术的结构验证。核心C还将准备所需的数量（最多 到毫克规模）的选定SPM，并将继续设计和合成选定的衍生物， 使他们能够进行生物学研究。核心C还将制备同位素取代的SPM衍生物， 作为SPM探针与核心B和项目1、2和3合作进行脂质组学分析，而其他 SPM探针将作为放射性标记衍生物的前体用于机理研究。核心C 将与项目1、2和3以及核心A-B合作开展涉及新型生物学的拟议研究， 的作用和细胞机制。 总的来说，这些合作研究将有助于阐明SPM的关键未开发功能， 帮助验证它们在炎症和组织再生的解决中的功能作用。

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.