The Synthesis of Certain Derivatives and Analogues of (-)- and (+)-Galanthamine and an Assessment of their Capacities to Inhibit Acetylcholine Esterase

J Org Chem. 2017 Aug 4;82(15):7869-7886. doi: 10.1021/acs.joc.7b01062. Epub 2017 Jul 24.

Abstract

Syntheses of certain di- and mono-oxygenated derivatives (e.g., 2 and 3, respectively) and analogues (e.g., 4, a D-ring monoseco-analogue of 2) of both the (-)- and (+)-enantiomeric forms of the alkaloid galanthamine [(-)-1] are reported. All have been assessed for their capacities to inhibit acetylcholine esterase but, in contrast to the predictions from docking studies, none bind strongly to this enzyme.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Animals
  • Cholinesterase Inhibitors / chemical synthesis
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Electrophorus
  • Galantamine / chemical synthesis
  • Galantamine / chemistry
  • Galantamine / pharmacology*
  • Molecular Conformation
  • Molecular Docking Simulation
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Cholinesterase Inhibitors
  • Galantamine
  • Acetylcholinesterase