Synthesis and evaluation of ent-Conduramine C-1 derivatives as α-glucosidase inhibitors via CSI-mediated amination reaction

Carbohydr Res. 2023 Feb:524:108746. doi: 10.1016/j.carres.2023.108746. Epub 2023 Jan 18.

Abstract

Concise synthesis of ent-conduramine C-1 and its derivatives has been achieved by using commercially available d-ribose. The key steps in the synthesis are regioselective and diastereoselective amination of polybenzyl ethers by chlorosulfonyl isocyanate (CSI), chelation-controlled carbonyl addition, and intramolecular olefin metathesis. All of the synthesized compounds were evaluated for inhibitory activity against α-glucosidase. The derivatives 18 (IC50 = 0.65 ± 0.03 mM) and 19 (IC50 = 0.26 ± 0.01 mM) were identified to be more potent than well-known α-glucosidase inhibitor acarbose (IC50 = 1.05 ± 0.17 mM) as a positive control.

Keywords: Amination; Chlorosulfonyl isocyanate; Conduramine; α-Glucosidase inhibitor.

MeSH terms

  • Amination
  • Glycoside Hydrolase Inhibitors* / pharmacology
  • Isocyanates*
  • Molecular Docking Simulation
  • Molecular Structure
  • Structure-Activity Relationship
  • alpha-Glucosidases

Substances

  • Glycoside Hydrolase Inhibitors
  • chlorosulfonyl isocyanate
  • Isocyanates
  • alpha-Glucosidases