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

“C-N、C-O 和 C-C 键形成反应以及生物活性化合物合成中的有机铋试剂。”

• 批准号: 416839-2012
• 负责人: Gagnon, Alexandre
• 金额: $ 2.55万
• 依托单位: Université du Québec à Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=596204
• 关键词: Organobismuth; reagents; bond; forming; reactions

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.

在药物相关化合物的制备中，能够有效地构建C-O、C-N和C-C键的新方法的发展是必不可少的。在生物活性分子上引入功能化的小的直链或环烷基团有助于探索它们的结合环境和微调与生物靶标的相互作用。此外，这项工作还可以优化化合物的生物物理性质，转化为候选药物的更好的药代动力学曲线。虽然有许多方法可以进行这种有机转化，但其中一些方法底物范围较小，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品。有机铋试剂在有机化学中得到了广泛的应用，部分原因是它们独特的反应活性以及与铋盐相关的低成本和毒性。目前的建议集中在开发新的合成方法，利用有机铋试剂在将高度官能化的烷基转移到药物化学中使用的特权支架上的独特反应性，如杂环、酚、酰胺和胺。这种方法可以方便地合成目前需要多步序列进行制备的化合物，从而在医药、工艺或农业化学中得到广泛的应用。参与这个研究项目的学生将学习最先进的技术以及相关的基本理论，为他们在工业或学术界的成功职业生涯做好准备。