Norpsilocin: freebase and fumarate salt
Acta Crystallographica Section E Crystallographic Communications – March 27, 2020
Source: OpenAlex
Summary
The precise 3D structure of psychedelics is paramount for drug design. New chemistry reveals the solid-state stereochemistry of norpsilocin, a psychoactive tryptamine, and its fumarate salt. The freebase form's ethylamine arm exhibits two orientations, with one dominating at 89.5% occupancy. This detailed structural understanding is vital for future psychedelic drug studies, informing how such compounds might interact with specific targets like nicotinic acetylcholine receptors, or how their stability could be influenced by free radicals and antioxidants in biological systems.
Abstract
The solid-state structures of the naturally occurring psychoactive tryptamine norpsilocin {4-hydroxy- N -methyltryptamine (4-HO-NMT); systematic name: 3-[2-(methylamino)ethyl]-1 H -indol-4-ol}, C 11 H 14 N 2 O, and its fumarate salt (4-hydroxy- N -methyltryptammonium fumarate; systematic name: bis{[2-(4-hydroxy-1 H -indol-3-yl)ethyl]methylazanium} but-2-enedioate), C 11 H 15 N 2 O + ·0.5C 4 H 2 O 4 2− , are reported. The freebase of 4-HO-NMT has a single molecule in the asymmetric unit joined together by N—H...O and O—H...O hydrogen bonds in a two-dimensional network parallel to the (100) plane. The ethylamine arm of the tryptamine is modeled as a two-component disorder with a 0.895 (3) to 0.105 (3) occupancy ratio. The fumarate salt of 4-HO-NMT crystallizes with a tryptammonium cation and one half of a fumarate dianion in the asymmetric unit. The ions are joined together by N—H...O and O—H...O hydrogen bonds to form a three-dimensional framework, as well as π–π stacking between the six-membered rings of inversion-related indoles (symmetry operation: 2 − x , 1 − y , 2 – z ).