基于含氟肽键构建的多肽设计合成

Due to the unique physicochemical properties of fluorine-containing groups, the efficient introduction of fluorine-containing groups under mild conditions is an important research direction of synthetic chemistry. In view of the important value of peptides in medicinal chemistry, biochemistry, etc., the design and synthesis of fluorinated peptides may produce special properties, functions and activities. Therefore, the efficient and highly selective introduction of fluorine-containing groups into peptides has important academic significance and application prospects, and also has great challenges. This project intends to develop a novel decarboxylation coupling reaction, which introduces important fluorine-containing functional groups (such as trifluoroethylamine, fluoroalkene group, etc.) into the polypeptide through the late derivatization of the carboxyl group in the polypeptide. To achieve controllable and selective construction of fluoropeptides, to construct a library of fluorinated peptide molecules, and to study their biological activities and drug functions. The completion of the project will help develop new synthetic methods for fluorinated peptides, provide efficient synthetic pathways and strategies for potentially bioactive fluoroorganic functional molecules, and study the structural and functional activities of fluorinated peptides. The relationship and development of fluorinated peptide drugs have important theoretical guiding significance and practical application value.

由于含氟基团独特的物理化学性质，在温和条件下实现对含氟基团的高效引入是合成化学的一个重要研究方向。鉴于多肽在药物化学、生物化学等方面的重要价值，设计并合成含氟多肽将可能产生特殊性质、功能和活性。因此，在多肽中高效、高选择性引入含氟基团具有重要的学术意义和应用前景，同时也存在巨大挑战。本项目拟开发新型脱羧偶联反应，通过多肽中羧基的后期功能衍生化，在多肽中引入重要含氟功能基团（如三氟乙胺、氟代烯烃这类生物电子等排体），实现对含氟多肽的可控和选择性构筑，构建含氟多肽分子库，进而研究其生物活性和药物功能。该项目的完成将有助于发展新的含氟多肽的合成方法学，为具有潜在生物活性的含氟有机功能分子提供有效的合成途径与策略，同时对研究含氟多肽的结构与功能活性的关系及含氟多肽药物的开发有着重要的理论指导意义和实际应用价值。

在本课题中，我们开展了对含官能团的偕二氟烯烃和单氟烯烃的合成研究，丰富和拓展了合成偕二氟烯烃和单氟烯烃的反应类型和催化体系。在发表的论文中，我们实现了对含胺基、内酰胺、脲、三氟甲基等官能团的偕二氟烯烃的合成，并且系统研究了反应的底物普适性和机理。在此基础上，我们利用偕二氟烯烃实现了铬催化的还原偶联反应，高效构建单氟烯烃产物。此类反应为合成β-氟烯丙醇类化合物提供了一个高效的方法。.在项目的资助下，我们共发表12篇SCI论文，其中关于氟化学领域的论文8篇，主要包括有Org.Lett., Org. Chem. Front., Chem. Commun.以及J. Org. Chen.等文章。培养研究生18名，其中已经毕业6名，研究生中获得国家奖学金1人，优秀毕业论文2人。.