碳青霉烯类β-内酰胺抗生素的化学合成及构效关系研究进展

Progress in chemical synthesis and structure-activity relationship of carbapenem β-lactam antibiotics

碳青霉烯是一类新型β-内酰胺抗生素,它具有广谱、耐酶等特点,已用于临床抗重症感染的治疗。骨架和侧链的化学合成是碳青霉烯类药物研究和开发的重点和热点方向。近年来,采用有机金属催化合成骨架、四氢吡咯烷与疏水基团相连接合成侧链,取得了一定的进展。未来合成研究所面临的最大挑战是提高碳青霉烯类β-内酰胺抗生素的生物活性,其策略是寻找有效的骨架合成途径,同时增加药物的脂溶性和稳定性。

Carbapenem is a new β-lactam antibiotic with broad antimicrobial spectrum and resistance to β-1actamase hydrolysis. Five carbapenems have been used to treat serious infections in clinical trials. Skeleton and chain syntheses have become highlights of study and development of new carbapenems. In recent years, various skeletal derivatives have been synthesized with organic metals as catalysts, and different side-chain derivatives have been obtained with the reaction of pyrrolidine and hydrophobic functional groups. In order to improve antimicrobial activities of carbapenems, the strategies are to explore new synthetic routes of the skeletons and side-chains and increase the hydrophobicity and stability of carbapenems.