New Metal-Catalyzed Allylic Substitution and Higher-Order Carbocyclization Reactions

新型金属催化烯丙基取代和高阶碳环化反应

• 批准号: 418236-2012
• 负责人: Evans, Andrew
• 金额: $ 7.36万
• 依托单位: Queen's University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=531056
• 关键词: New; Metal; Catalyzed; Allylic; Substitution

The construction of architecturally challenging structural motifs in a predictable and expeditious manner remains a Grand Challenge for synthetic organic chemistry. This limitation has severely limited the ability to facilitate Structure-Activity Relationship Studies in a range of biologically interesting molecules, which has limited the exploitation of many interesting and potentially useful lead compounds. Natural products have historically proven reliable lead compounds for drug discovery. For example, these agents have inspired over 60% of the anticancer agents and 70% of the antibiotics entering clinical trials in the last 30 years. Nevertheless, many companies have abandoned natural products due to the perceived problems associated with the preparation of libraries of natural product analogues for detailed Structure Activity Relationship Studies. Transition metal-catalyzed reactions facilitate the construction of structural motifs that are generally not accessible via conventional methods making these reactions an extremely powerful tool for target directed synthesis. Nevertheless, many of the developments in this area involve tedious catalyst tuning and optimization of reaction conditions. We believe that a combined theoretical/experimental approach will expedite this process by delineating the origin of selectivity and thereby provide solutions to longstanding problems in a manner that would be infinitely more challenging through empirical studies. Hence, in contrast to enzymes, which evolve through multiple iterations, i.e. evolutionary development, this approach should expedite catalyst identification and development by providing insight into new chemical reactivity. We anticipate that this program will result in the development of state-of-the-art transformations that facilitate the construction of complex molecules in an efficient, selective and atom-economical manner. Hence, this work will expand the current "tool-kit" of chemical reactions, which will facilitate the construction of biologically important structures in a more expeditious manner and provide cutting-edge HQP training.

以可预测和快速的方式构建具有挑战性的结构基序仍然是合成有机化学的巨大挑战。 这种限制严重限制了在一系列生物学上感兴趣的分子中促进结构-活性关系研究的能力，这限制了许多感兴趣的和潜在有用的先导化合物的开发。 天然产物在历史上被证明是药物发现的可靠先导化合物。 例如，在过去的30年中，这些药物激发了超过60%的抗癌药物和70%的抗生素进入临床试验。 然而，许多公司已经放弃了天然产品，由于与制备天然产品类似物的文库相关的问题，用于详细的结构活性关系研究。 过渡金属催化的反应促进了结构基序的构建，这些结构基序通常不能通过常规方法获得，使得这些反应成为用于靶向合成的极其强大的工具。 然而，该领域的许多发展涉及繁琐的催化剂调节和反应条件的优化。 我们相信，结合理论/实验的方法将加快这一进程，划定选择性的起源，从而提供解决方案，长期存在的问题的方式，这将是无限更具挑战性的经验研究。 因此，与通过多次迭代（即进化开发）进化的酶相反，这种方法应该通过提供对新化学反应性的洞察来加速催化剂的鉴定和开发。 我们预计，这一计划将导致发展国家的最先进的转换，促进复杂分子的建设，在一个有效的，选择性和原子经济的方式。 因此，这项工作将扩大目前的化学反应“工具包”，这将有助于以更快的方式构建生物学上重要的结构，并提供尖端的HQP培训。