Psilacetin derivatives: fumarate salts of the methyl–ethyl, methyl–allyl and diallyl variants of the psilocin prodrug

Acta Crystallographica Section E Crystallographic Communications  – January 08, 2021

Source: OpenAlex

Summary

The precise molecular architecture of psychedelic compounds is fundamental to medicinal chemistry. Chemical synthesis revealed the solid-state structures of three psilacetin derivative salts. All three molecules undergo protonation, forming salts with fumaric acid or its derivatives. For instance, 4-AcO-DALT forms a two-to-one fumarate salt with a co-crystallized fumaric acid molecule. Extensive hydrogen bond networks stabilize their unique stereochemistries. This fundamental chemistry advances drug studies on alkaloids, offering insights for understanding various receptors, like nicotinic acetylcholine receptors.

Abstract

The solid-state structures of the salts of three psilacetin derivatives, namely, 4-acetoxy- N -ethyl- N -methyltryptammonium (4-AcO-MET) hydrofumarate {systematic name: [2-(4-acetyloxy-1 H -indol-3-yl)ethyl](methyl)ethylazanium 3-carboxyprop-2-enoate}, C 15 H 21 N 2 O 2 + ·C 4 H 3 O 4 − , 4-acetoxy- N -allyl- N -methyltryptammonium (4-AcO-MALT) hydrofumarate {systematic name: [2-(4-acetyloxy-1 H -indol-3-yl)ethyl](methyl)prop-2-enylazanium 3-carboxyprop-2-enoate}, C 16 H 21 N 2 O 2 + ·C 4 H 3 O 4 − , and 4-acetoxy- N , N -diallyltryptammonium (4-AcO-DALT) fumarate–fumaric acid (1/1) (systematic name: bis{[2-(4-acetyloxy-1 H -indol-3-yl)ethyl]diprop-2-enylazanium} but-2-enedioate–( E )-butenedioic acid (1/1)), 2C 18 H 23 N 2 O 2 + ·C 4 H 2 O 4 2− ·C 4 H 4 O 4 , are reported. All three salts possess a protonated tryptammonium cation. The 4-AcO-MET and 4-AcO-MALT compounds are charge-balanced by 3-carboxyacrylate (hydrofumarate) anions. The 4-AcO-DALT complex crystallizes as a two-to-one tryptammonium-to-fumarate salt, which co-crystallizes with a fumaric acid molecule. Each structure is consolidated by N—H...O and O—H...O hydrogen bonds.

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