Analytical characterisation of the routes by thermolytic decarboxylation from tryptophan to tryptamine using ketone catalysts, resulting in tetrahydro-β-carboline formation

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 41; no. 3; pp. 872 - 882
• Main Authors: Brandt, Simon D., Mansell, David, Freeman, Sally, Fleet, Ian A., Alder, John F.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 07-06-2006; Elsevier Science
• Subjects: Analysis; Analytical chemistry; Analytical, structural and metabolic biochemistry; Biological activities; Biological and medical sciences; Carbolines - chemical synthesis; Carboxylic Acids - chemistry; Decarboxylation; Fingerprint; Forensic; Fundamental and applied biological sciences. Psychology; Gas Chromatography-Mass Spectrometry; General pharmacology; Hallucinogens; Ketones - chemistry; Magnetic Resonance Spectroscopy; Medical sciences; Pharmacology. Drug treatments; Spectrometry, Mass, Electrospray Ionization; Synthesis; Tetrahydro-β-carbolines; Tryptamines; Tryptamines - chemistry; Tryptophan - chemistry; Analytical chemistry; Fingerprint; Synthesis; Biological activities; Tetrahydro-β-carbolines; Decarboxylation; Forensic; Tryptamines; Hallucinogens; Tryptamine; Tryptophan; Biosynthesis; Biological activity; Tetrahydro-p-carbolines; Aminoacid; Fingerprint method; Hallucinogen
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2006.02.007

N-Alkylated tryptamines have complex psychoactive properties. Routes for clandestine synthesis are described on Internet websites one of which involves the thermolytic decarboxylation of tryptophan to tryptamine as a precursor to psychoactive compounds. High boiling solvents and ketone catalysts have been employed to facilitate the decarboxylation of tryptophan.
The present study has revealed that there is formation of tetrahydro-β-carboline (THBC) derivatives which may originate from reaction with both the solvent and the ketone catalyst. The application of gas chromatography electron- and chemical-ionisation ion trap tandem mass spectrometry (GC–IT-MS–MS), in combination with nuclear magnetic resonance (NMR), led to the isolation and identification of 1,1-disubstituted-tetrahydro-β-carbolines formed as major impurities in the tryptamine. Confirmation was by synthesis of the THBC derivatives from tryptamine using Pictet-Spengler cyclisation. Under EI-conditions, mass spectral characterisation of the THBCs suggests predominance of alkyl cleavage.
These impurities will yield a useful profile for identification of the synthetic pathway and likely reagents employed, particularly a “fingerprint” of the ketone catalyst and an insight into the influence of solvents and catalysts on the formation of by-products.