7-[(2S)-2-氨甲基-1-吡咯烷基]-喹诺酮衍生物的合成及体外抗菌活性  

Synthesis and in vitro antibacterial activity of 7-[(2s)-2-amino methyl-pyrrolidine-1-yl]-quinolone derivatives

作　　者：陈胜昔[1] 郭慧元[1] 

机构地区：[1]中国医学科学院协和医科大学医药生物技术研究所,北京100050

出　　处：《中国抗生素杂志》2004年第7期397-400,422,共5页Chinese Journal of Antibiotics

摘　　要：为寻找具有广谱抗菌活性的新喹诺酮类化合物 ,本文以 L-脯氨酸为原料 ,经甲酯化 ,苄基 (Bz)保护 ,氨解 ,L i Al H4 还原 ,叔丁氧羰基 (BOC)保护 ,脱苄基 ,然后与不同的喹诺酮母环化合物缩合 ,最后脱去叔丁氧羰基等 8步反应制得目标化合物 ,其结构经1 H- NMR,FAB- MS确证。本文共制得 16个化合物 ,对其中 5个 (13～ 17)目标化合物进行体外抗菌活性测定的结果表明 ,化合物 15对肺炎链球菌的体外活性相当于对照药加替沙星而优于环丙沙星 ,对其余菌株的活性总体上看则低于对照品。其余 4个目标化合物总体上看其活性均低于对照品 。To design and synthesize a series of new quinolones which would provide improved Gram-positive antibacterial activity, while retaining the good Gram-negative activity. The substance, L-proline (1), was reacted with MeOH to give 2, then reacted with BzCl to give 3; 3 reacted with NH 3·H 2O to afforded 4, which was reduced by LiAlH 4 to give 5, 5 was protected by BOC to afford 6, which reacted with H 2 to give 7. Compound 7 was condensed with five quinolone nucleus to obtain 8～12. At last, the BOC groups were hydrolyzed to give 13～17. In this article, twelve unreported compounds (6～17) were synthesized. The in vitro antibacterial activity of five target compounds (13～17) were tested against 10 Gram-positive and 10 Gram-negative organisms. The compound 15 (MIC 0.12μg/ml) showed an excellent activity against S.pneumoniae, which was consistent with gatifloxacin (MIC 0.12μg/ml), but better than ciprofloxacin (MIC 0.5～2 μg/ml). Nevertheless, the compound 15 (MIC 0.5～32μg/ml) showed lower activity against other organisms than gatifloxacin (MIC 0.03～2μg/ml). All the other four compounds (13, 14, 16 ,17) (MIC 0.25～>64 μg/ml) showed lower activity than gatifloxacin and ciprofloxacin.

关 键 词：喹诺酮 合成 抗菌活性 

分 类 号：R978.1[医药卫生—药品]