New Metal-Catalyzed Reactions for the Synthesis of Bioactive Agents

用于合成生物活性剂的新金属催化反应

• 批准号: RGPIN-2022-04075
• 负责人: Evans, PAndrew
• 金额: $ 7.5万
• 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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=747860
• 关键词: New; Metal; Catalyzed; Reactions; Synthesis

Alchemy represents the origin of synthetic chemistry, which envisioned producing valuable and functional products from readily available and inexpensive starting materials. Consequently, the ongoing desire to prepare value-added compounds with unique functionality aided by the development of new spectroscopic techniques to characterize and confirm their identity led to the evolution of the modern chemical and pharmaceutical industries. Nevertheless, despite these enormous advances, the ability to manufacture metric tons of critical materials in a robust and efficient manner remains an ongoing challenge, with an ever-increasing emphasis on the environmental impact of the processes. For example, the challenges associated with developing and manufacturing drugs highlight synthetic chemistry's current strengths and weaknesses. A recent study revealed that the increasing cost of drug discovery, which is ascribed to the low success rate of clinical candidates progressing through the various phases of drug development (0.2%), is attributed to the relatively simple nature of the drugs. The outcome of this inefficient process is that the average cost to market a new drug now exceeds $1.3 billion (CAD) and that only one out of ten drugs generate enough revenue to cover the research and development costs. The study also concludes that more complex structures improve the successful transition from a lead to a commercial entity. Nevertheless, the increased complexity mandates the development of new, more sophisticated synthetic processes to expand the repertoire of methods that can be deployed for their preparation. GOAL: We plan to develop new chemical reactions that facilitate the construction of challenging structural motifs that are not easily accessible by more conventional methods. The proposal will also address the critical and ongoing challenges that limit the scope of the chemistry, which can be ascribed to the lack of insight into the fundamental problem. We have a longstanding program in developing new catalytic reactions using theoretical and mechanistic understanding to provide unique solutions to challenging problems and address important knowledge gaps. We anticipate that this proposal will make significant strides in developing and understanding new methods that facilitate the construction of complex molecules in an efficient, selective and atom-economical manner. IMPACT: The proposal is expected to expand the current "toolkit" of chemical reactions by developing innovative and cutting-edge synthetic methods, thereby providing the HQP with a world-class training environment. The proposed work is highly collaborative, giving the HQP opportunities to work at the interface of chemistry and biology. This unique training environment is expected to enhance Canada's reputation in synthetic organic chemistry by disseminating the work in the form of high-profile publications, news articles and seminars by the HQP.

炼金术代表了合成化学的起源，它设想用容易获得且廉价的原材料生产有价值的功能性产品。因此，人们不断渴望制备具有独特功能的增值化合物，并通过开发新的光谱技术来表征和确认其身份，从而导致了现代化学和制药工业的发展。然而，尽管取得了这些巨大的进步，以稳健和高效的方式制造公吨关键材料的能力仍然是一个持续的挑战，人们越来越重视这些过程对环境的影响。例如，与开发和制造药物相关的挑战凸显了合成化学当前的优势和劣势。最近的一项研究表明，药物发现成本的增加是由于药物开发各个阶段的临床候选药物的成功率较低（0.2%），而药物的性质相对简单。这种低效流程的结果是，一种新药的平均营销成本现在超过 13 亿美元 (CAD)，而且只有十分之一的药物能产生足够的收入来支付研发成本。该研究还得出结论，更复杂的结构可以提高从领先企业到商业实体的成功转型。然而，复杂性的增加要求开发新的、更复杂的合成工艺，以扩大可用于其制备的方法库。目标：我们计划开发新的化学反应，以促进具有挑战性的结构基序的构建，而这些基序是通过更传统的方法难以实现的。该提案还将解决限制化学范围的关键和持续的挑战，这可以归因于缺乏对基本问题的洞察。我们有一个长期计划，利用理论和机理的理解来开发新的催化反应，为具有挑战性的问题提供独特的解决方案并弥补重要的知识差距。我们预计该提案将在开发和理解新方法方面取得重大进展，这些新方法有助于以高效、选择性和原子经济的方式构建复杂分子。影响：该提案预计将通过开发创新和尖端的合成方法来扩展当前的化学反应“工具包”，从而为总部提供世界一流的培训环境。拟议的工作具有高度协作性，为总部提供了在化学和生物学交叉领域开展工作的机会。这种独特的培训环境预计将通过总部以高调出版物、新闻文章和研讨会的形式传播工作，从而提高加拿大在合成有机化学领域的声誉。