新一代氟喹诺酮类抗菌素——巴洛沙星的合成  

Synthesis of balofloxacin,the forth generation fluoroquinolone

作　　者：王道林[1] 姜莉莉[1] 李春芳[1] 

机构地区：[1]北京理工大学化工与环境学院,北京100081

出　　处：《中国药物化学杂志》2005年第6期340-343,共4页Chinese Journal of Medicinal Chemistry

摘　　要：目的合成新一代氟喹诺酮类抗菌素———巴洛沙星。方法以1-环丙基-6,7-二氟-1,4-二氢-8-甲氧基-4-氧代喹啉-3-羧酸为起始原料,在硼酸酯的作用下与3-甲胺基哌啶二醋酸盐缩合得到目标产物———巴洛沙星。以3-氨基吡啶为原料,分别通过甲酰化反应、氢化铝锂还原和原甲酸三乙酯缩合、硼氢化钠还原两种方法得到3-甲胺基吡啶,最后经催化氢化得到中间体3-甲胺基哌啶。结果合成巴洛沙星的总收率为60%,两种方法合成3-甲胺基哌啶的总收率分别为16%和32%。结论改进了合成路线,降低了成本,有助于巴洛沙星的合成。Aim To synthesize the forth generation fluoroquinolone balofloxacin. Method Balofloxacin was synthesized by condensation of 1-cyclopropyl-6, 7-difluoro-1, 4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid with 3-methylaminopiperidine in the presence of trimethoxyborane. The key intermediate 3- methylaminopiperidine was synthesized from 3-methylaminopyridine by two methods, formylation and lithium aluminium hydride reduction or condensation with triethyl orthoformate and sodium borohydride reduction, and then hydrolysis. Its chemical structure was identified with ^1H-NMR and IR. Results The structure was identified by spectra. The over all yield of balofloxacin was 60 %, the two methods to the synthesis of 3- methylaminopyridine with the overall yield of 16% and 32%. Conclusions The synthetic method is improved and the cost is reduced. It is available to the synthesis of balofloxacin.

关 键 词：药物化学 药物制备 化学合成 巴洛沙星 氟喹诺酮 3-甲胺基哌啶 

分 类 号：R914.5[医药卫生—药物化学]