"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。”

基本信息

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

项目摘要

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.

允许有效地构建C-O，C-N和C-C键的新方法解体对于制备药物相关化合物至关重要。生物活性分子上功能化的小线性或环状烷基的掺入有助于探索其结合环境以及与生物学靶标相互作用的微调。此外，此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动力学特征。尽管存在许多执行这种有机转化的方法，但其中一些方法患有较差的底物范围，需要复杂的配体/催化剂系统，或者需要昂贵的试剂，在某些情况下会产生有毒的侧产品。 Organobsuth试剂在有机化学中发现了广泛的应用，部分原因是它们的独特反应性以及与鞭毛盐相关的低成本和毒性。当前的提案着重于开发新的合成方法论，这些方法可以利用有机晶剂试剂在将高度功能化烷基基团转移到用于药用化学中的特权支架上的独特反应性，例如杂环，苯酚，胺和胺。这样的方法应通过允许当前需要多步序列的化合物合成药物，过程或农业化学来找到广泛的应用。参与该研究计划的学生将学习最先进的技术以及相关的基本理论，为他们的工业或学术界成功做好准备。