Application of Acyl Aminals in Target and Function Oriented Synthesis

本项目将利用无环n -酰基动物在一系列重要应用中的效用。n -酰基动物是通过冗长的标准方案制备的，但通过最近开发的多组分反应从腈中获得它们，可以获得比以前更大的结构多样性。这种多组分反应将应用于构建一个通过以前的方法难以获得的pederin类似物库，以尽量减少这种有效的免疫抑制剂和细胞毒性。n -酰基动物将在研究中用作n -酰基离子的前体，这些研究将验证使用毛细管微反应器快速筛选手性酸催化反应的效率和机制。设计n -酰基动物的能力，通过可预测的刺激裂解和释放生物活性分子，将用于设计新的药物输送载体。通过这个奖项，有机和大分子化学项目支持了匹兹堡大学化学系Paul Floreancig教授的研究。弗洛朗西教授的研究工作围绕着新化学反应的开发和机理分析以及生物活性分子的合成。这项研究将为高效合成具有可调性质的分子提供新的机会。这些项目的成功发展将对制药和农业工业的铅的产生和合成产生影响。

This project will exploit the utility of acyclic N-acyl aminals in a range of important applications. N-Acyl aminals have been prepared through lengthy standard protocols but their availability from nitriles through a recently developed multicomponent reaction allows for access to greater structural diversity than has previously been available. This multicomponent reaction will be applied to the construction of a library of pederin analogs that would be difficult to access through previous approaches in an effort to minimize the toxicity of this potent immunosuppressive and cytotoxic agent. N-Acyl aminals will be used as precursors to N-acyliminium ions in studies that will validate the use of a capillary-based microreactor for rapidly screening the efficiency and mechanism of chiral acid catalyzed reactions. The capacity to design N-acyl aminals that cleave and release biologically active molecules through predictable stimuli will be utilized in the design of new drug delivery vehicles. With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Paul Floreancig of the Department of Chemistry at the University of Pittsburgh. Professor Floreancig's research efforts revolve around the development and mechanistic analysis of new chemical reactions and the synthesis of biologically active molecules. This research will provide new opportunities for efficient syntheses of molecules that have tunable properties. Successful development of these projects will have an impact on lead generation and synthesis in the pharmaceutical and agricultural industries.