Bildung, Kristallstruktur und absolute Konfiguration von (−)‐N‐(Chloromethyl)galanthaminium‐chlorid

Abstract

Formation, X-Ray Crystal Structure, and Absolute Configuration of (-)-N-(Ch1oromethyl)galanthaminium ChlorideThe acetylcholinesterase inhibitor galanthamine (l), main alkaloid of several Narcissus species, readily forms a quaternary ammonium salt by reaction with the solvent CH2C12. The structure and absolute configuration of (-)-N-(chloromethyl)galanthaminiurn 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,) contain two crystallographically independent cations which do not differ significantly from one another. The CH2CI 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 C1-anion or to the C1-atom of an adjacent cation.

Hydrogen-bonding properties of galanthamine: an investigation through crystallographic database observations and computational chemistry

“…1). Neutral galanthamine corresponds to the first one, (1) (Carroll et al, 1990), the remaining eight to charged derivatives, (2)-(9) (Hemetsberger et al, 2004;Carroll et al, 1990;Hirnschall et al, 2003;Roques et al, 1980;Peeters et al, 1997;Matusch et al, 1994). Tables 2 and 3 gather Table 2 Geometric parameters of conventional HB observed in the crystal structures of galanthamine derivatives found in the CSD.…”

“…(iii) the Cl atoms of the NCH 2 Cl moiety (Matusch et al, 1994;YILTUI refcode). Table 2 shows that the intermolecular HB are significantly shorter than the intramolecular interactions.…”

The Amaryllidaceae alkaloids: an untapped source of acetylcholinesterase inhibitors

“…On the other hand, four independent measurements of the AChE inhibitory activity of undulatine have shown RA values between 5.48 and 13.82 indicating that the compound is a strong AChE inhibitor. N-Chloromethylgalanthamine, reported as natural compound (Zhu et al 2015), has RA value of 2.28, but it may be considered as an artifact of isolation procedure (Matusch et al 1994). Compounds from all of the tested skeleton types have representatives in the group of moderate AChE inhibitors (Fig.…”