New Metal-Catalyzed Reactions for the Synthesis of Bioactive Agents

炼金术代表了合成化学的起源，它设想从容易获得和廉价的起始材料生产有价值的和功能性的产品。因此，通过开发新的光谱技术来表征和确认其身份，不断希望制备具有独特功能的增值化合物，这导致了现代化学和制药工业的发展。然而，尽管有这些巨大的进步，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，对过程的环境影响越来越重视。例如，与开发和制造药物相关的挑战突出了合成化学目前的优势和劣势。最近的一项研究表明，药物发现的成本不断增加，这是由于临床候选药物在药物开发的各个阶段的成功率较低（0.2%），这是由于药物相对简单的性质。这一低效过程的结果是，现在销售一种新药的平均成本超过13亿美元（CAD），而每10种药物中只有一种产生足够的收入来支付研发成本。该研究还得出结论，更复杂的结构有助于从领先企业向商业实体的成功过渡。然而，复杂性的增加要求开发新的、更复杂的合成过程，以扩大可用于其制备的所有方法。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，这些结构基序不容易通过更传统的方法获得。该提案还将解决限制化学范围的关键和持续挑战，这些挑战可归因于对根本问题缺乏洞察力。我们有一个长期的计划，在开发新的催化反应，利用理论和机理的理解，提供独特的解决方案，以挑战性的问题，并解决重要的知识差距。我们预计，这一提议将在开发和理解新方法方面取得重大进展，这些方法有助于以高效，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目前的化学反应“工具包”，从而为HQP提供世界级的培训环境。拟议的工作是高度协作的，使HQP有机会在化学和生物学的接口工作。这种独特的培训环境有望通过HQP的高调出版物、新闻文章和研讨会的形式传播工作，提高加拿大在合成有机化学方面的声誉。

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.