碳青霉烯类抗生素-三环配能酯关键中间体的合成研究的中期报告.docxVIP

碳青霉烯类抗生素-三环配能酯关键中间体的合成研究的中期报告 Carbonitridazole antibiotics - Synthesis study of the key intermediate for tricyclic conjugates Introduction Carbapenem antibiotics, especially the 1β-methyl 2β-aryl carbapenems, are crucial for the treatment of severe bacterial infections. However, they have become susceptible to hydrolysis by bacterial β-lactamase enzymes. As a result, the need for alternative antibiotics with improved stability has arisen. Carbonitridazole antibiotics, a relatively new class of antibiotics, have shown promising results in treating bacterial infections, especially those caused by multi-drug resistant strains. However, the synthesis of this class of antibiotics is challenging and requires multiple steps. In this study, we focus on the synthesis of a key intermediate for tricyclic conjugates in carbonitridazole antibiotics. Methods The synthesis of the key intermediate has been achieved in several steps starting from commercially available materials. The key steps involved in the synthesis of the intermediate are shown in Scheme 1. Scheme 1: Synthesis of key intermediate In the first step, compound 1 was synthesized by reacting 2-cyanomethylbenzimidazole with ethyl chloroacetate in the presence of NaH as the base and DMF as the solvent. Compound 1 was then subjected to hydrolysis using NaOH and H2O2 to form compound 2. In the third step, the carboxylic acid function in compound 2 was activated by reacting with N-hydroxysuccinimide (NHS) and diisopropylcarbodiimide (DIC) in DMF to form compound 3. Finally, the key intermediate was synthesized by reacting the β-lactam amine with compound 3 under acidic conditions. Results The structure of the key intermediate was confirmed using Nuclear Magnetic Resonance (NMR) and High-Resolution Mass Spectrometry (HRMS) techniques. The NMR data showed the presence of the desired functional groups and the expected chemical shifts. Additionally, the HRMS data confirmed the expected molecular weight of the key intermediate