"Organobismuth reagents in C-N, C-O, and C-C bond forming reactions and synthesis of biologically active compounds."

新方法的发展使得C-O， C-N和C-C键的有效构建在制备药学相关化合物中是必不可少的。在生物活性分子上加入功能化的小线性或环烷基，有助于探索它们的结合环境，并微调与生物靶标的相互作用。此外，该练习允许优化化合物的生物物理特性，转化为改进的候选药物的药代动力学特征。虽然有许多方法可以进行这种有机转化，但其中一些方法的底物范围很差，需要复杂的配体/催化剂系统，或者需要昂贵的试剂，在某些情况下，还会产生有毒的副产物。有机铋试剂在有机化学中有广泛的应用，部分原因是其独特的反应性以及与铋盐相关的低成本和低毒性。目前的建议侧重于开发新的合成方法，利用有机铋试剂在将高功能化烷基转移到用于药物化学的特殊支架上的独特反应性，如杂环、酚、酰胺和胺。这些方法可以方便地合成目前需要多步骤序列来制备的化合物，因此应该在医药、工艺或农业化学中有广泛的应用。参与这项研究计划的学生将学习最先进的技术以及相关的基础理论，为他们在工业界或学术界的成功职业生涯做好准备。

The development of new methododologies that allow the efficient construction of C-O, C-N, and C-C bonds is essential in the preparation of pharmaceutically relevant compounds. The incorporation of functionalized small linear or cyclic alkyl groups on bioactive molecules facilitates the exploration of their binding environment and the fine tuning of interactions with the biological target. In addition, this exercise allows the optimization of the biophysical properties of the compounds, translating into improved pharmacokinetic profiles for the drug candidate. While many methods exist to perform such organic transformations, some of them suffer from poor substrate scope, require complex ligand/catalyst systems or necessitate reagents that are expensive and, in some cases, generate toxic side products. Organobismuth reagents have found wide applications in organic chemistry, in part due to their unique reactivity and the low cost and toxicity associated with bismuth salts. The current proposal focuses on the development of new synthetic methodologies that exploit the unique reactivity of organobismuth reagents in the transfer of highly functionalized alkyl groups onto privileged scaffolds used in medicinal chemistry, such as heterocycles, phenols, amides, and amines. Such methods should find broad applications in medicinal, process, or agricultural chemistry, by allowing the expedient synthesis of compounds which currently require multi-step sequences for their preparation. Students involved in this research program will learn state-of-the-art techniques as well as the related fundamental theory, preparing them for a successful career in industry or academia.