Synthesis and Analytical Characterization of 1-(1,2-Dimethylcyclobutane-1-Carbonyl)-Lysergic Acid Diethylamide...

Lysergic acid diethylamide (LSD) analogues have emerged as new psychoactive substances (NPS) since the mid-2010s, and novel derivatives continue to appear on the recreational drug market. Since late 2022, products marketed as "1D-LSD" have been advertised on X (formerly Twitter) and other websites. Despite various online references portraying 1D-LSD as 1-(1,2-dimethylcyclobutane-1-carbonyl)-LSD, our chemical analysis of a product marketed as "1D-LSD" revealed that it actually contained 1-(thiophene-2-carbonyl)-LSD (1T-LSD), which has the same nominal mass. Another group subsequently reported similar findings in a blotter paper printed "1D-LSD.". In this study, we synthesized 1D-LSD as a mixture of four diastereomers, reflecting the stereoisomers of the commercially available 1,2-dimethylcyclobutane-1-carboxylic acid. The mixture was separated into two groups, each consisting of two diastereomers, through preparative liquid chromatography. The correspondence between the fractions and diastereomers was established using nuclear magnetic resonance spectroscopy aided by quantum chemical calculations. The synthesized 1D-LSD was further characterized using liquid chromatography/mass spectrometry, gas chromatography/mass spectrometry, and Fourier-transform infrared spectroscopy. Additionally, the incorporated carboxylic acid was recovered through alkaline hydrolysis, and analysis of the recovered acid confirmed the presence of all four diastereomers. The analytical properties of 1D-LSD were compared with those of 1T-LSD. Our comparative analysis revealed that the two compounds exhibited markedly different analytical properties, indicating that confusion between them is unlikely when appropriate analytical methods are applied.