The first example of palladium-catalyzed cascade amidine arylation-intramolecular ester amidation for the synthesis of hypoxanthines: application to the synthesis of 8-azanebularine analogues

Org Biomol Chem. 2017 Jan 4;15(2):379-386. doi: 10.1039/c6ob02121b.

Abstract

8-Azanebularine analogues display interesting antiviral, antitumour and biochemical activities. However, typical glycosylation of 8-azapurines always resulted in the desired products in low yields due to the lack of stereo- and regioselectivity of the glycosylation reaction. Herein, a concise synthetic route toward 8-azanebularine analogues has been developed. Key steps involve a copper-catalyzed 1,3-dipolar cycloaddition of a 1-β-azido sugar moiety with ethyl 3-bromopropiolate and a palladium-catalyzed cascade amidine arylation-intramolecular ester amidation reaction to build the hypoxanthine structural motif. This protocol affords a facile methodology for the synthesis of a series of novel 8-azanebularine analogues from the readily accessible 1-β-azido sugar moiety under mild conditions.

MeSH terms

  • Amidines / chemistry*
  • Catalysis
  • Esters / chemistry*
  • Hypoxanthines / chemical synthesis*
  • Hypoxanthines / chemistry
  • Molecular Conformation
  • Palladium / chemistry*
  • Purine Nucleosides / chemical synthesis*
  • Purine Nucleosides / chemistry
  • Ribonucleosides / chemical synthesis*
  • Ribonucleosides / chemistry

Substances

  • 8-azanebularine
  • Amidines
  • Esters
  • Hypoxanthines
  • Purine Nucleosides
  • Ribonucleosides
  • Palladium