10.1021/jo1015807
The research focuses on the development of a concise and convergent four-step synthesis method for PA-824, a promising antituberculosis drug candidate. The purpose of this study was to improve upon the existing synthetic route used for large-scale production of PA-824, addressing concerns related to cost, safety, and efficiency. The new approach offers significant improvements by utilizing a safe alternative to the explosive 2,4-dinitroimidazole and a functionalized pseudosymmetrical glycidol derivative. Key chemicals used in the synthesis include (R)-3-chloro-1,2-propanediol, p-methoxybenzoyl chloride, 4-(trifluoromethoxy)benzyl alcohol, 2-chloro-4-nitroimidazole, and potassium hydroxide. The synthesis process culminates in the production of PA-824 with high yield and enantiomeric excess, demonstrating the potential for kilogram-scale production. The conclusions of the research highlight the efficiency, simplicity, and safety of the new synthetic method, which is crucial for the future production and distribution of affordable TB treatments, especially in developing regions where the disease is most prevalent.
