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

在这个GOALI（与工业界学术联络的赠款机会）项目中，由化学部的化学结构，动力学机制B计划支持，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，这需要一种综合的方法来发现变革性的解决方案。具体目标是开发一种新的温度扫描反应（TSR）协议，用于监测化学过程，这将适用于工业和学术实验室。待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。 这种新方法通过提供对反应过程和化学反应机理的更深入理解来提高安全性和效率。作为一个更广泛的目标，这项研究为有机合成，合成方法学，催化和反应工程的未来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（D3 SC）计划。与GOALI计划要求相适应，该项目涉及来自斯克里普斯和四个工业合作伙伴布里斯托迈尔斯施贵宝，辉瑞，默克和Abbvie的跨学科团队;预计这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。随着真实的实时监测反应能力的不断扩大，以及测量工具的准确性和数据密度的增加，化学家面临着开发数据捕获和解释的综合方法的挑战，沿着新的反应分析工具的创建。该项目旨在开发一种新型的温度扫描反应（TSR）协议和反应器，用于简化使用温度作为制药工艺研究相关反应中的可变动力学参数。该方法有望促进：a）基础机理研究; B）药物/发现化学中的快速初始筛选;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化学合成中的当前挑战所决定的。 具体反应类别包括：a）不对称氢化; B）电催化转化; c）光氧化还原催化;和d）非贵金属催化转化。这些研究旨在评估和开发这种温度扫描反应（TSR）方法的背景下，反应进程动力学分析（RPKA），一种方法，早期开发的首席研究员。这项研究通过提供对工业反应过程的更好理解来提高安全性和效率。新的动力学分析方法可以广泛应用于整个化学，以提高基本的机理理解。 该项目的竞争前性质确保了没有知识产权的考虑将妨碍工业和学术参与者之间的公开讨论。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估的支持。

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.