How to Develop Organometallic Catalytic Reactions in the Pharmaceutical Industry
How to Develop Organometallic Catalytic Reactions in the Pharmaceutical Industry
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DOI：
10.1021/acs.oprd.3c00086
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发表时间：
2023-05-03
影响因子：
3.4
通讯作者：
Farina, Vittorio
中科院分区：
文献类型：
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作者：
Farina, Vittorio
通过对最近文献的仔细分析，似乎清楚的是，在API合成中使用的许多过渡金属催化过程是在不诉诸任何种类的动力学分析的情况下开发的。即使承认其中一些过程是为早期开发项目开发的，不需要彻底优化，但缺乏动力学工作是令人惊讶的。这一观点表明，除了利用现代技术，如高通量实验（HTE）和经典的优化工具，如实验设计（DOE），适度的动力学分析是必要的，以开发真正有效的催化反应。我们提供了一些基本的理论考虑，并提出了一些相当简单的工具，可以用来集成到API开发的催化步骤的动力学分析。
From a careful analysis of the recent literature, it seems clear that many transition-metal-catalyzed processes used in API synthesis are developed without resorting to any kind of kinetic analysis. Even acknowledging that some of these processes were developed for early development projects and did not need to be thoroughly optimized, the lack of kinetic work is surprising. This Perspective suggests that, in addition to the utilization of modern technologies such as high-throughput experimentation (HTE) and classical optimization tools such as Design of Experiments (DOE), a modest level of kinetic analysis is necessary to develop truly effective catalytic reactions. We offer some basic theoretical considerations and suggest some rather simple tools which can be employed to integrate kinetic analysis of catalytic steps into API development.