Late‐Stage Functionalization and Characterization of Drugs by High‐Throughput Desorption Electrospray Ionization Mass Spectrometry
Abstract
Late‐stage functionalization (LSF) of drug molecules is an approach to generate modified molecules that retain functional groups present in the active drugs. Here, we report a study that seeks to characterize the potential value of high‐throughput desorption electrospray ionization mass spectrometry (HT DESI‐MS) for small‐scale rapid LSF. In conventional route screening, HT‐based DESI‐MS provides contactless, rapid analysis, reliable and reproducible data, minimal sample requirement, and exceptional tolerance to high salt concentrations. Ezetimibe (E), an established hypertension drug, is targeted for modification by LSF. C−H alkenylation and azo‐click reactions are utilized to explore this approach to synthesis and analytical characterization. The effect of choice of reactant, stoichiometry, catalyst, and solvent are studied for both reactions using high throughput DESI‐MS experiments. Optimum conditions for the formation of LSF products are established with identification by tandem mass spectrometry (MS/MS).
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 01, 2022
- Source ID
- 10.1002/cplu.202100449
Entities
People
- Jyotirmoy Ghosh
- Kai‐Hung Huang
- R. Graham Cooks
- Shiqing Xu
Organizations
- Defense Advanced Research Projects Agency
- National Science Foundation
- Purdue University
- Yusuf Hamied Department of Chemistry