D3SC: GOALI: Development of a Temperature Scanning Reaction Protocol for Pharmaceutical Catalytic Reaction Screening and Optimization

在这个由化学部化学结构、动态和机制B计划支持的GALI(学术与工业联系机会)项目中，斯克里普斯研究所的Donna Blackmond教授和AbbVie的Shashank Shekhar博士正在开发新的方法来研究复杂化学反应的速率和机制。这项研究解决了与制药工业相关的复杂有机反应的现代研究中固有的挑战和机遇，需要采取综合方法来发现变革性的解决方案。具体目标是开发一种用于监测化学过程的新的温度扫描反应(TSR)协议，该协议将适用于工业和学术实验室。需要详细研究的反应在化学合成中具有广泛的兴趣，但具有复杂的动力学和机理。这一新的方法通过提供对反应过程和化学反应机理的更深层次的了解，提高了安全性和效率。作为一个更广泛的目标，这项研究为未来在有机合成、合成方法学、催化和反应工程方面的创新提供了一个平台。该项目需要开发新的数据丰富的实验工具，部分资金来自数据驱动的化学发现科学(D3SC)倡议。根据GOALI计划的要求，该项目涉及来自斯克里普斯和四个工业合作伙伴百时美施贵宝、辉瑞、默克和Abbvie的跨学科团队；这预计将促进学术和工业实验室之间的未来合作。该项目的另一个主要目标是为研究生和本科生提供培训，包括在工业环境中的经验。随着实时监测反应的能力的扩大，以及测量工具的准确性和数据密度的增加，化学家们面临着开发一种集成的数据捕获和解释方法以及创建新的反应分析工具的挑战。该项目旨在开发一种新的温度扫描反应(TSR)方案和反应器，以简化在与制药过程研究相关的反应中将温度作为可变动力学参数的使用。这种方法有望推动：a)基础机理研究；b)药物药物/发现化学中的快速初步筛选；以及c)药物制造中的工艺优化。这些研究的反应类别的选择是由制药工业和一般化学合成的当前挑战决定的。具体的反应类别包括：a)不对称氢化；b)电催化转化；c)光氧化还原催化；d)非贵金属催化转化。这些研究的目的是在反应进度动力学分析(RPKA)的背景下评估和开发这种温度扫描反应(TSR)方法，RPKA是由首席调查员早期开发的一种方法。这项研究通过提供对工业反应过程的更好的理解来提高安全性和效率。动力学分析的新方法可以广泛应用于整个化学领域，以加强对基本机理的理解。该项目的竞争前性质确保任何知识产权考虑因素都不会阻碍产业界和学术界参与者之间的公开讨论。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

In this GOALI (Grant Opportunities for Academic Liaison with Industry) project, supported by the Chemical Structure, Dynamic & Mechanism B Program of the Chemistry Division, Professor Donna Blackmond at the Scripps Research Institute and Dr. Shashank Shekhar of AbbVie are developing new methods to study the rates and mechanisms of complex chemical reactions. This research addresses challenges and opportunities inherent in the modern study of complex organic reactions related to the pharmaceutical industry, which warrant an integrated approach in order to discover transformative solutions. The specific goal is to develop a new Temperature Scanning Reaction (TSR) protocol for monitoring chemical processes, which will be applicable in both industrial and academic laboratories. Reactions to be studied in detail are of broad interest in chemical synthesis but have complex kinetics and mechanisms. This new methodology enhances safety and efficiency by providing a deeper understanding of reaction processes and the mechanisms of chemical reactions. As a broader goal, this research provides a platform for future innovations in organic synthesis, synthetic methodology, catalysis, and reaction engineering. This project requires the development of new data-rich experimental tools and is partially funded through the Data-Driven Discovery Science in Chemistry (D3SC) initiative. Commensurate with the GOALI program requirements, the project involves an interdisciplinary team from Scripps and the four industrial partners Bristol Myers Squibb, Pfizer, Merck and Abbvie; this is expected to foster future collaboration between academic and industrial laboratories. Another major goal of this project is to provide training for graduate and undergraduate students, including experience in an industrial setting.With the expanding ability to monitor reactions in real time, and as the accuracy and data-density of measuring tools increases, chemists face the challenge of developing an integrated approach for data capture and interpretation, along with the creation of new reaction analysis tools. This project seeks to develop a novel Temperature-Scanning Reaction (TSR) protocol and reactors for streamlining the use of temperature as a variable kinetic parameter in reactions relevant to pharmaceutical process research. This approach is expected to advance: a) fundamental mechanistic study; b) rapid initial screening in pharmaceutical medicinal/discovery chemistry; and c) process optimization in pharmaceutical manufacture. The choice of reaction classes for these investigations is informed by current challenges in the pharmaceutical industry and chemical synthesis in general. Specific reaction classes include: a) asymmetric hydrogenation; b) electrocatalytic transformations; c) photoredox catalysis; and d) non-precious metal catalytic transformations. These studies aim to evaluate and develop this Temperature Scanning Reaction (TSR) approach in the context of Reaction Progress Kinetic Analysis (RPKA), a method developed earlier by the lead Principal Investigator. This research enhances safety and efficiency by providing an improved understanding of industrial reaction processes. New methodology for kinetic analysis can be broadly applied across chemistry to enhance fundamental mechanistic understanding. The pre-competitive nature of this project ensures that no intellectual property considerations will hamper the open discussion among industrial and academic participants.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.