[Analysis of the key intermediates for the regioselectivity control in the methylation of the manufacture of clarithromycin by reversed-phase high performance liquid chromatography].
2',4''-O-Bis(trimethylsilyl)erythromycin A-9-O-(1-isopropoxycyclohexyl)oxime (2',4''-TMS-EMIPCH) and 2',4''-O-bis(trimethylsilyl)-6-O-methylerythromycin A-9-O-(1-isopropoxycyclohexyl)oxime (2',4"-TMS-IPCH) are the key intermediates for manufacturing clarithromycin. A qualitative and quantitative method for baseline separation of E- and Z-isomers and related process substances has been established. A DIKMA-Inertsil ODS-3 column (150 mm x 4.6 mm i.d., 5 microm) was used. The column temperature was maintained at 40 degrees C. The mobile phase was CH3CN-H2O (95:5, v/v). The flow rate was 1.5 mL/min and the detection wavelength was UV 205 nm. Good linearities for E-2',4''-TMS-EMIPCH and E-2',4''-TMS-IPCH were obtained in the ranges of 6-60 microg (r = 0.9994) and 6-72 microg (r = 0.9998), respectively. The method described has also been demonstrated to work equally well on other 2',4''-O-bis(trimethylsilyl)erythromycin 9-oxime hydroxyl derivatives, which provided the criterion for optimizing the protective groups at 9-oxime hydroxyl position and the study of regioselectivity of methylation at the 6-OH position.
Liang
Jianhua
J
School of Life Science and Technology, Beijing Institute of Technology, Beijing 100081, China. ljhbit@bit.edu.com
Yao
Guowei
G
Zheng
Shaojun
S
D000900:Anti-Bacterial Agents / Q000032:analysis* / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D056148:Chromatography, Reverse-Phase / Q000379:methods; D017291:Clarithromycin / Q000032:analysis* / Q000737:chemistry*; D008745:Methylation; D015394:Molecular Structure; D010091:Oximes / Q000032:analysis / Q000737:chemistry
D000900:Anti-Bacterial Agents; D010091:Oximes; D017291:Clarithromycin