Radiosynthesis of [14C]acarbose

Arzneimittelforschung. 1989 Oct;39(10):1251-3.

Abstract

Acarbose (O-4,6-dideoxy-4-[[(1S, 4R, 5S, 6S)-4,5,6-trihydroxy-3- (hydroxymethyl)-2-cyclohexen-1-yl]amino]-a-D-glucopyranosyl-(1---- 4)-O-a-D- glucopyranosyl-(1----4)-4-glucopyranose, Bay g 5421), an a-glucosidase inhibitor from Actinoplanes, has been developed for the treatment of diabetes mellitus. To investigate the pharmacokinetics and the biotransformation, 14C-labelled acarbose ([14C]Bay g 5421) was required. About 37 GBq (1 Ci) D-[U-14C]glucose was used as a precursor to obtain [14C]acarbose with a radiochemical yield of between 1.58 and 2.56%. For fermentation purposes resting cells of the Actinoplanes mutant SN 1667/47 were used under cometabolism conditions with a 10-fold excess of maltose. The specific radioactivities achieved in individual preparations were 7.77 MBq/mg (210 microCi/mg), 8.03 MBq/mg (217 microCi/mg), and 9.14 MBq/mg (247 microCi/mg), with a radiochemical purity of greater than 98% in each case. By hydrolysis and subsequent investigation of the hydrolysis products it was shown that [14C]carbon atoms originating from the radioactive glucose are present only in the core and not in the maltose unit of [14C]acarbose.

MeSH terms

  • Acarbose
  • Actinomycetales / metabolism
  • Chromatography, High Pressure Liquid
  • Chromatography, Thin Layer
  • Culture Media
  • Fermentation
  • Hydrolysis
  • Isotope Labeling
  • Radiochemistry
  • Sucrase / antagonists & inhibitors
  • Trisaccharides / metabolism*
  • Trisaccharides / pharmacology

Substances

  • Culture Media
  • Trisaccharides
  • Sucrase
  • Acarbose