Chromatography System for Organic Synthesis-Administrative Supplements for Equipment Purchases

总结 有机化合物的氟化影响物理化学性质，这在医学环境中会干扰 在体外和体内的药效学、药代动力学、分布和/或代谢特征。因此 在温和条件下选择性地安装氟化基团的能力对于获得新的治疗方法是至关重要的 和生物探针。然而，氟化基质和/或试剂的独特物理性质通常不适合于本发明的组合物。 干扰基本的有机反应，这可能使合成序列复杂化，以获得氟化的 化合物.因此，许多常规的有机反应在氟化试剂存在下根本不起作用， 与氟化基材。此外，氟化基质的独特性质使新的反应性 这是相应的无氟对应物无法实现的， 创新的反应和策略，用于访问医学相关的子结构 通过这个R35项目，Altman集团的长期目标是开发创新的催化剂系统， 试剂和/或用于获得医学相关的氟化亚结构的合成策略。在这一领域， 我们使用创新的策略（例如电化学，C- H官能化，脱氧氟烷基化，过渡金属催化反应），使合成化学家， 将简单和容易获得的官能团（例如醇、羰基、氟化烯烃）转化为广泛的 非常有价值的氟化类似物的光谱。此外，我们探索合成变换，其中 氟化的亚结构通过不同的机理反应和/或以不同的选择性提供产物 相对于非氟化底物的类似反应。拟议战略的制定将使 药物化学家获得新的和独特的生物探针和治疗。第二个长期目标是 探索可能影响药物稳定性的氟化亚结构赋予的物理化学扰动， 分布，代谢和/或配体-蛋白质相互作用，并将这些原则应用于下一个- 产生具有改进的药物样性质的氟化治疗候选物。在我们下一阶段的工作中， 我们将应用现代创新的合成反应，提供下一代天然的氟化类似物， 将保留有治疗价值的药效学作用并且还改善稳定性的产品， 相对于母体化合物的分布。

SUMMARY Fluorination of an organic compound affects physicochemical properties, which in medicinal settings perturbs pharmacodynamic, pharmacokinetic, distribution, and/or metabolic profiles both in vitro and in vivo. Thus, the ability to selectively install fluorinated groups under mild conditions is essential for accessing new therapeutics and biological probes. However, the unique physical properties of fluorinated substrates and/or reagents typically perturb fundamental organic reactivities, which can complicate synthetic sequences to access fluorinated compounds. Thus, many routine organic reactions simply do not work in the presence of fluorinated reagents or with fluorinated substrates. Additionally, the unique properties of fluorinated substrates enable new reactivities that cannot be achieved by the respective non-fluorinated counterparts, which provides opportunities to develop innovative reactions and strategies for accessing medicinally relevant substructures With this R35 program, the Altman group has a long-term goal of developing innovative catalyst systems, reagents, and/or synthetic strategies for accessing medicinally relevant fluorinated substructures. In this area, we develop fluorination and fluoroalkylation methodologies using innovative strategies (e.g. electrochemistry, C– H functionalization, deoxyfluoroalkylation, transition metal catalyzed reactions) that enable synthetic chemists to convert simple and readily available functional groups (e.g. alcohols, carbonyls, fluorinated alkenes) into a broad spectrum of highly valuable fluorinated analogs. Additionally, we explore synthetic transformations in which fluorinated substructures react through distinct mechanisms and/or deliver products with distinct selectivities relative to analogous reactions of nonfluorinated substrates. Development of the proposed strategies will enable medicinal chemists to access new and unique biological probes and therapeutics. A second long-term goal is to explore physicochemical perturbations imparted by fluorinated substructures that might influence drug stability, distribution, metabolism, and/or ligand-protein interactions, and to apply such principles in the design of next- generation fluorinated therapeutic candidates with improved drug-like properties. In the next phase of our work, we will apply modern innovative synthetic reactions to deliver next-generation fluorinated analogs of natural products that will retain the therapeutically valuable pharmacodynamic action and also improve stability and distribution relative to the parent compounds.