The synthesis of (14)C-labeled, (13)CD2-labeled saxagliptin, and its (13)CD2-labeled 5-hydroxy metabolite

J Labelled Comp Radiopharm. 2014 Mar;57(3):136-40. doi: 10.1002/jlcr.3179. Epub 2014 Feb 12.

Abstract

(14)C-labeled saxagliptin, (13) CD2-labeled saxagliptin, and its (13) CD2-labeled 5-hydroxy metabolite were synthesized to further support development of the compound for biological studies. This paper describes new syntheses leading to the desired compounds. A total of 3.0 mCi of (14)C-labeled saxagliptin was obtained with a specific activity of 53.98 μCi/mg (17.13 mCi/mmol). The radiochemical purity determined by HPLC was 99.29%, and the overall radiochemical yield was 3.0% based upon 100 mCi of [(14)C]CH2 I2 starting material. By following similar synthetic routes, 580.0 mg of (13)CD2-labeled saxagliptin and 153.1 mg of (13)CD2-labeled 5-hydroxysaxagliptin metabolite were prepared.

Keywords: 13C-label; 14C-label; deuterium; isotope labeling; saxagliptin; type 2 diabetes.

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / chemical synthesis
  • Adamantane / chemistry
  • Adamantane / metabolism
  • Carbon Isotopes / chemistry
  • Carbon Radioisotopes / chemistry
  • Chemistry Techniques, Synthetic
  • Dipeptides / chemical synthesis*
  • Dipeptides / chemistry*
  • Dipeptides / metabolism

Substances

  • 5-hydroxysaxagliptin
  • Carbon Isotopes
  • Carbon Radioisotopes
  • Dipeptides
  • saxagliptin
  • Adamantane