[Analysis of the key intermediates for the regioselectivity control in the methylation of the manufacture of clarithromycin by reversed-phase high performance liquid chromatography]

Se Pu. 2004 May;22(3):237-40.
[Article in Chinese]

Abstract

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.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / analysis*
  • Anti-Bacterial Agents / chemistry*
  • Chromatography, High Pressure Liquid* / methods
  • Chromatography, Reverse-Phase* / methods
  • Clarithromycin / analysis*
  • Clarithromycin / chemistry*
  • Methylation
  • Molecular Structure
  • Oximes / analysis
  • Oximes / chemistry

Substances

  • Anti-Bacterial Agents
  • Oximes
  • Clarithromycin