Norpsilocin: freebase and fumarate salt

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]-1H-indol-4-ol}, C11H14N2O, and its fumarate salt (4-hydroxy-N-methyltryptammonium fumarate; systematic name: bis{[2-(4-hydroxy-1H-indol-3-yl)ethyl]methylazanium} but-2-enedioate), C11H15N2O+·0.5C4H2O4 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).

Structure–Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice

“…53 This biotransformation reaction probably also occurs with secondary amines like 4-acetoxy-N-methyltryptamine (4-AcO-NMT) and quaternary ammoniums like 4acetoxy-N,N,N-trimethyltryptamine (4-AcO-TMT), the synthetic analogues of baeocystin and aeruginascin. 41,43,54 Importantly, psilacetin is less potent than psilocin in producing psychedelic-like effects in rodents, 52,55 which is consistent with the expected profile of a prodrug. As with the other constituents of psilocybin-containing mushrooms, the pharmacology of 4-acetoxy analogues of psilocybin, baeocystin, and aeruginascin is largely uncharacterized, and a side-by-side comparison of the natural products and their corresponding active metabolites has not been performed.…”

“…More recently, psilacetin has emerged as a popular new psychoactive substance (NPS) on recreational drug markets, where it is sold as a psilocybin alternative. − Analogous to the metabolism of psilocybin to psilocin, 4-acetoxy compounds are thought to hydrolyze to their corresponding 4-hydroxy compounds. ,, While definitive biotransformation studies in animals are lacking, in vitro evidence from liver microsomes supports the metabolic conversion of 4-acetoxy compounds to their 4-hydroxy analogues . This biotransformation reaction probably also occurs with secondary amines like 4-acetoxy- N -methyltryptamine (4-AcO-NMT) and quaternary ammoniums like 4-acetoxy- N , N , N -trimethyltryptamine (4-AcO-TMT), the synthetic analogues of baeocystin and aeruginascin. ,, Importantly, psilacetin is less potent than psilocin in producing psychedelic-like effects in rodents, , which is consistent with the expected profile of a prodrug. As with the other constituents of psilocybin-containing mushrooms, the pharmacology of 4-acetoxy analogues of psilocybin, baeocystin, and aeruginascin is largely uncharacterized, and a side-by-side comparison of the natural products and their corresponding active metabolites has not been performed.…”

5-MeO-DALT: the freebase of N,N-diallyl-5-methoxytryptamine

“…The title compound is similar to that of other 5-O-substituted tryptamines whose structures have been reported, including bufotenine (BUFTEN: Falkenberg, 1972a), melatonin (MELATN: Wakahara et al, 1972), 5-MeO-DMT hydrochloride (MOTYPT: Falkenberg & Carlströ m, 1971), 5-methoxytryptamine (MXTRUP: Quarles et al, 1974), 5-MeO-DMT and 5-methoxymonomethyltryptamine (QQQAGY & QQQAHA: Bergin et al, 1968). The structure is also similar to the freebases of other psychedelic tryptamines that have been reported, including psilocybin (PSILOC: , psilocin (PSILIN: , N,N-dimethyltryptamine (DMTRYP: Falkenberg, 1972b), N-methyl-N-propyltryptamine (WOHYAW: Chadeayne, et al 2019) and norpsilocin (Chadeayne et al, 2020).…”

5-Methoxy-N,N-di-n-propyltryptamine (5-MeO-DPT): freebase and fumarate

“…and norpsilocin(CCDC 1992279;Chadeayne et al, 2020b), and the synthetic psychedelic N-methyl-N-n-propyltryptamine (WOHYAW;Chadeayne et al, 2019b). The other fumarate salts of tryptamines known are norpsilocin(CCDC 1992278;Chadeayne et al, 2020b), 4-hydroxy-N-methyl-N-isopropyltryptamine(CCDC 1962339;Chadeayne et al, 2020a), 5-methoxy-2,N,N-trimethyltryptamine and psilacetin (HOCJUH;Chadeayne et al, 2019a).…”