Analytical Research & Development, MRL, Merck & Co., Inc., West Point, PA 19486, USA.
Process Research & Development, MRL, Merck & Co., Inc., West Point, PA 19486, USA.
Int J Pharm. 2022 Jan 5;611:121324. doi: 10.1016/j.ijpharm.2021.121324. Epub 2021 Nov 27.
The use of protection groups to shield a functional group during a synthesis is employed throughout many reactions and organic syntheses. The role of a protection group can be vital to the success of a reaction, as well as increase reaction yield and selectivity. Although much work has been done to investigate the addition of a protection group, the removal of the protection group is just as important - however, there is a lack of methods employed within the literature for monitoring the removal of a protection group in real time. In this work, the process of removing, or deprotecting, a ketal protecting group is investigated. Process analytical technology tools are incorporated for in situ analysis of the deprotection reaction of a small molecule model compound. Specifically, Raman spectroscopy and Fourier transform infrared spectroscopy show that characteristic bands can be used to track the decrease of the reactant and the increase of the expected products over time. To the best of our knowledge, this is the first report of process analytical technology being used to monitor a ketal deprotection reaction in real time. This information can be capitalized on in the future for understanding and optimizing pharmaceutically-relevant deprotection processes and downstream reactions.
在许多反应和有机合成中，使用保护基团在合成过程中屏蔽官能团。保护基团的作用对于反应的成功至关重要，同时还可以提高反应收率和选择性。尽管已经做了大量工作来研究保护基团的添加，但保护基团的去除同样重要——然而，文献中缺乏用于实时监测保护基团去除的方法。在这项工作中，研究了酮缩醛保护基团的去除或脱保护过程。过程分析技术工具被纳入原位分析小分子模型化合物的脱保护反应。具体而言，拉曼光谱和傅里叶变换红外光谱表明，可以使用特征谱带随时间跟踪反应物的减少和预期产物的增加。据我们所知，这是首次报道使用过程分析技术实时监测酮缩醛脱保护反应。未来，可以利用这些信息来理解和优化与制药相关的脱保护过程和下游反应。
