摘要
以3-甲基-9,10-二氟-7-氧代-2,3-二氢-7H-吡啶并[1,2,3-de][1,4]苯并噁嗪-6-羧酸乙酯(3)为原料,经亲核取代、脱羧、环合、水解、Hofmann降解可制得帕珠沙星消旋体(1),总收率25.1%。并建立了HPLC法分离1的光学异构体。采用Zorbax C18柱,甲醇-手性溶液(8mmol/L L-苯丙氨酸和4mmol/L硫酸铜混合溶液,用NaOH溶液调至pH3.5)(15∶85)为流动相,检测波长为324nm,光学异构体可被良好分离,检测限2ng。
The (3S) racemate of pazufloxacin (1) was synthesized from ethyl 3-methyl-9,10-difluoro-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylate (3) by nucleophilic substitution and decarboxylation,followed by cyclization,hydrolysis and Hofmann degradation with an overall yield of 25.1%. A HPLC method forresolution the enantiomers of 1 was established. A Zorbax C18 column was used with the mobile phase of methanol-chiralsolution(containing 8mmol/L L-phenylalanine and 4mmol/L cupric sulfate, adjusted to pH 3.5 by NaOH solution) (15∶85)at the detection wavelength of 324nm. The detection limit was 2ng.
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2004年第6期321-323,共3页
Chinese Journal of Pharmaceuticals
