FORMATION, X-RAY CRYSTAL-STRUCTURE, AND ABSOLUTE-CONFIGURATION OF (-)-N-(CHLOROMETHYL)GALANTHAMINIUM CHLORIDE

The acetylcholinesterase inhibitor galanthamine (1), main alkaloid of several Narcissus species, readily forms a quaternary ammonium salt by reaction with the solvent CH2Cl2. The structure and absolute configuration of (-)-N-(chloromethyl)galanthaminium chloride (2) were determined by X-ray diffraction (R = 0.075 for 2775 observed independent reflexions) and NMR spectroscopy. The tetragonal crystals (space group P4(3)) contain two crystallographically independent cations which do not differ significantly from one another. The CH2Cl group is attached to the quaternary N-atom in stereospecific (R)-configuration. In the crystal, the configurational position of the Me group at the N-atom of 2 differs from that of the crystalline free base 1. Hydrogen bonding is observed from the OH group at C(3) of 2 to the Cl(-)anion or to the Cl-atom of an adjacent cation.