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

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-beta-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-beta-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.

Analytical chemistry of synthetic routes to psychoactive tryptamines. Part III. Characterisation of the Speeter and Anthony route to N,N-dialkylated tryptamines using CI-IT-MS-MS.

Twelve symmetrically and 13 asymmetrically N,N-disubstituted glyoxalylamide precursors and their corresponding tryptamine derivatives have been characterised by gas chromatography low-pressure chemical ionisation ion trap tandem mass spectrometry (CI-IT-MS-MS) with internal (in situ) ionisation using methanol as the chemical ionisation reagent. Mass spectral differences and similarities between the investigated compounds are discussed and put into context with previous investigations. In tryptamines the formation of [CH2=N+R2R3] iminium ions after beta-cleavage appears to be the dominating process. Dissociation of the protonated molecule into [3-vinylindole]+ for example, appears to be a minor pathway when compared with electrospray triple quadrupole tandem mass spectrometry (ESI-TQ-MS-MS) where this ion transition was found to be of distinctive importance. CI-IT-MS-MS is also found to enable the differentiation between most isomeric derivatives studied.

Analytical chemistry of synthetic routes to psychoactive tryptamines. Part II. Characterisation of the Speeter and Anthony synthetic route to N,N-dialkylated tryptamines using GC-EI-ITMS, ESI-TQ-MS-MS and NMR.

The degree of alkylation of the side chain nitrogen in tryptamines is one important factor that affects psychoactivity. The method of Speeter and Anthony is considered to be one of the most important synthetic preparative methods. The final step in this reaction is based on the reduction of a (substituted) indole-3-yl-glyoxalylamide to the desired tryptamine with metal hydride. Twelve symmetrically and 13 asymmetrically N,N-disubstituted glyoxalylamides and their corresponding tryptamine derivatives have been synthesised and characterised by gas chromatography EI-ion trap mass spectrometry, electrospray-triple quadrupole-tandem mass spectrometry and NMR spectroscopy. Mass spectral and NMR similarities and differences between the investigated compounds are discussed. A solvent dependency is observed that has to be taken into consideration for the unambiguous assignment of (1)H- and (13)C-NMR chemical shifts. The (1)H-NMR study demonstrated that one can evaluate the rotamer populations of the asymmetrical glyoxalylamides. In a forensic or clinical scenario where single or multiple reaction monitoring approaches are contemplated, the appropriate ion transitions of choice may then focus on the two main fragmentations, namely beta-cleavage ([M+H](+)-->CH(2)N(+)R(2)R(3)) and/or alpha-cleavage ([M+H](+)-->[3-vinylindole](+)), respectively. The synthesis, NMR and MS analytical data presented provide the forensic analyst and clinical biochemist with a detailed and self-consistent body of information and mechanisms for the spectral identification of the more likely psychoactive tryptamines that may be met.

Analytical chemistry of synthetic routes to psychoactive tryptamines. Part I. Characterisation of the Speeter and Anthony synthetic route to 5-methoxy-N,N-diisopropyltryptamine using ESI-MS-MS and ESI-TOF-MS.

5-Methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT), a new psychoactive tryptamine derivative, has been synthesised by the Speeter and Anthony procedure. This synthetic route was characterised by ESI-MS-MS, ESI-TOF-MS and NMR. Side products have been identified as 3-(2-N,N-diisopropylamino-ethyl)-1H-indol-5-ol (5), 2-N,N-diisopropylamino-1-(5-methoxy-1H-indol-3-yl)-ethanol (6), 2-(5-methoxy-1H-indol-3-yl)-ethanol (7) and 2-N,N-diisopropylamino-1-(5-methoxy-1H-indol-3-yl)-ethanone (8).