Synthesis and synthetic process optimization of the enterovirus 71 3C protease inhibitor NK-1.8k / 国际药学研究杂志

ABSTRACT

Objective: To synthesize the enterovirus 71 3C protease inhibitor NK-1.8k and optimize the synthetic process. Methods: With N-Boc-L-glutamic acid dimethyl ester as the starting material, the target compound NK-1.8k was synthesized via the substitution, reductive amination, deprotection, amide condensation, hydrolysis, and reduction reactions. Compared with the original synthetic route, the tandem string type in the important intermediate 5 synthesis was changed to parallel type, thereby the total synthetic reactions were condensed from seven steps to six steps, and some post-processing methods were also optimized. Results: The structures of intermediates and the target compound were confirmed by MS and 1H NMR data, and the total yield of the target compound synthesis was increased to 13.3% from 10.7% of the original route. Conclusion: The synthetic route established in this article for NK-1.8k is reasonable and feasible, the raw materials used are cheap and easily available, the operation is simple, most of the reaction conditions are mild and controllable, the post-processing is simple, the intermediates are easy to separate and purify, the steps are short, and the yield is high. This method provides a valuable reference for the further synthesis of NK-1.8k and similar products.