Preparation of 2R, 3S, 2'R-nadolol enantiomer using S-(-)-menthyl chloroformate as a chiral derivatizing reagent

Arch Pharm Res. 2010 Sep;33(9):1301-6. doi: 10.1007/s12272-010-0902-1. Epub 2010 Oct 9.

Abstract

Stereoisomers of nadolol were derivatized with S-(-)-menthyl chloroformate((-)-MCF) forming their diastereomers, RSR-nadolol-(-)-MCF, SRS-nadolol-(-)-MCF, RRS-nadolol-(-)-MCF and SSRnadolol-(-)-MCF. Diastereomeric mixture were then chromatographically resolved by preparative HPLC (JAIGEL-ODS-BP-L, 500 × 25 mm column) eluted with methanol-water (84:16, v/v) at flow rate 2.5 mL/min. RSR-nadolol-(-)-MCF diastereomer was hydrolyzed with 5% LiOH at 80°C for 48 h, and the decomposed mixture was further purified by semi-preparative HPLC. The purity and final yield of RSR-nadolol were 99.97% and 12.95%, respectively.

MeSH terms

  • Adrenergic beta-Antagonists / chemistry*
  • Adrenergic beta-Antagonists / isolation & purification*
  • Chromatography, High Pressure Liquid
  • Formates / chemistry*
  • Hot Temperature
  • Hydrolysis
  • Indicators and Reagents / chemistry*
  • Isomerism
  • Magnetic Resonance Spectroscopy
  • Nadolol / chemistry*
  • Nadolol / isolation & purification*
  • Spectrometry, Mass, Electrospray Ionization
  • Spectroscopy, Fourier Transform Infrared
  • Tandem Mass Spectrometry
  • Technology, Pharmaceutical / methods
  • Time Factors

Substances

  • Adrenergic beta-Antagonists
  • Formates
  • Indicators and Reagents
  • menthyl chloroformate
  • Nadolol