Microwave‐accelerated synthesis of psychoactive deuterated N,N‐dialkylated‐[α,α,β,β‐d4]‐tryptamines

Brandt, Simon D.; Tirunarayanapuram, Sri Subha; Freeman, Sally; Dempster, Nicola M.; Barker, Steven A.; Daley, Paul F.; Cozzi, Nicholas V.; Martins, Cláudia P.B.

doi:10.1002/jlcr.1557

Cited by 15 publications

(15 citation statements)

References 32 publications

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“…This was most probably caused by either insufficient separation or low abundance of the other isomers. These metabolites were further hydroxylated to two dihydroxy metabolites (9, 10) and these finally to two trihydroxy metabolites (12,13) at the indole ring, respectively. Furthermore, a ring-rearranged metabolite (6) could be formed after aliphatic hydroxylation in section 2.…”

Section: -F-daltmentioning

confidence: 99%

“…The present study describes the biotransformation and detectability of three ring substituted DALT derivatives 5-fluoro-DALT (5-F-DALT), 7-methyl-DALT (7-Me-DALT), and 5,6-methylenedioxy-DALT (5,6-MD-DALT), which were synthesized in advance of potential distribution as NPS [12]. As Cozzi and Daley [13] described pharmacological potency for 5-substitued DALTs and Wagmann et al the inhibition of the monoamine oxidase A (publication in preparation) it can be assumed that such compounds will appear once on the drugs of abuse market.…”

Section: Introductionmentioning

confidence: 99%

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Biotransformation and detectability of the new psychoactive substances N,N-diallyltryptamine (DALT) derivatives 5-fluoro-DALT, 7-methyl-DALT, and 5,6-methylenedioxy-DALT in urine using GC-MS, LC-MSn, and LC-HR-MS/MS

et al. 2016

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Derivatives of N,N-diallyltryptamine (DALT) can be classified as new psychoactive substances. Biotransformation and detectability of 5-fluoro-DALT (5-F-DALT), 7-methyl-DALT (7-Me-DALT), and 5,6-methylenedioxy-DALT (5,6-MD-DALT) are described here. Their metabolites detected in rat urine and pooled human liver microsomes were identified by liquid chromatography (LC)-high resolution (HR)-tandem mass spectrometry (MS/MS). In addition, the human cytochrome-P450 (CYP) isoenzymes involved in the main metabolic steps were identified and detectability tested in urine by the authors' urine screening approaches using GC-MS, LC-MS n ,or LC-HR-MS/MS. Aromatic and aliphatic hydroxylations, N-dealkylation, N-oxidation, and combinations could be proposed for all compounds as main pathways. Carboxylation after initial hydroxylation of the methyl group could also be detected for 7-Me-DALT and O-demethylenation was observed for 5,6-MD-DALT. All phase I metabolites were extensively glucuronidated or sulfated. Initial phase I reactions were catalyzed by CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5. Rat urine samples were analyzed following two different low dose administrations. GC-MS was not able to monitor consumption reliably, but all three drugs are predicted to be detectable in cases of overdose. The LC-MS n and LC-HR-MS/MS approaches were suitable for detect an intake of all three compounds mainly via their metabolites. However, after the lowest dose, a reliable monitoring could only be achieved for 5-F-DALT via LC-MS n and LC-HR-MS/MS and for 7-Me-DALT via LC-HR-MS/MS. The most abundant targets in both LC-MS screenings were one of two hydroxy-aryl metabolites and both corresponding glucuronides for 5-F-DALT, one N-deallyl hydroxy-aryl, the carboxy, and one dihydroxy-aryl metabolite for 7-Me-DALT, and the demethylenyl metabolite, its oxo metabolite, and glucuronide for 5,6-MD-DALT.

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Section: -F-daltmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Biotransformation and detectability of the new psychoactive substances N,N-diallyltryptamine (DALT) derivatives 5-fluoro-DALT, 7-methyl-DALT, and 5,6-methylenedioxy-DALT in urine using GC-MS, LC-MSn, and LC-HR-MS/MS

et al. 2016

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“…Restricted rotation in indole‐3‐yl‐ N , N ‐dialkyl glyoxalylamides results in the detection of syn‐periplanar and anti‐periplanar rotamers leading to two sets of side chain related peaks when using NMR spectroscopy. In addition, asymmetrically disubstituted glyoxalylamides have previously been shown to display predominant peaks that corresponded to one of the rotamers . As far as 5‐methoxy‐2‐methylindole‐3‐yl‐ N , N ‐dialkyl glyoxalylamides were concerned two sets of rotamers were also detected and the extent to which this occurred is reflected in unequal proton integrals reported in the NMR section.…”

Section: Resultsmentioning

confidence: 99%

“…Synthesis procedures of all 13 precursors and tryptamine products were adapted from previous work . This was based on the Speeter and Anthony approach that provides convenient access to a large variety of simple tryptamines.…”

Section: Methodsmentioning

confidence: 93%

“…The use and origin of solvents and reagents, and details on instrumentation, i.e. 1D/2D NMR, GC‐EI‐MS, and GC‐CI‐MS/MS, have been described previously . However, 5‐methoxy‐2‐methylindole (99%) and N ‐allylmethylamine (96%) were purchased from Aldrich (Dorset, UK) and GC separations were carried out using a 30 m × 0.25 mm (0.25 µm film thickness) DB1ms column (J&W).…”

Section: Methodsmentioning

confidence: 99%

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Synthesis and characterization of 5‐methoxy‐2‐methyl‐N,N‐dialkylated tryptamines

Brandt

Tearavarich

Dempster

et al. 2012

Drug Testing and Analysis

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The absence of reference material is a commonly experienced difficulty among medical and forensic professionals tasked with identifying new psychoactive substances that are encountered for the first time. The identification of newly emerging substances lies at the heart of forensic and clinical analysis, and a proactive public health policy calls for a thorough analysis of the properties of new psychoactive substances before they appear in the emergency clinic, where they may be noticed because of adverse reactions or toxicity. For example, a wide range of N,N-dialkyltryptamines show psychoactive properties in humans and these tryptamines are sometimes encountered as intoxicants. However, most of the existing reference data on new psychoactive tryptamines have been obtained retrospectively, after reports of acute toxicities. To address the need for reference standards for new tryptamines, thirteen 5-methoxy-2-methyl-N,N-dialkyltryptamines were prepared. Analytical characterization was based on ¹H and ¹³C nuclear magnetic resonance (NMR), gas chromatography-electron ionization ion-trap mass spectrometry (GC-EI-IT-MS) and chemical ionization-ion-trap tandem mass spectrometry (CI-IT-MS/MS), respectively. Differentiation among isomers was feasible by NMR and MS. In addition to the expected iminium ion base peak, indole-related key ions were detected under EI-IT-MS conditions at m/z 174, 159, 131, 130, and 103. CI-IT-MS/MS analysis of the 5-methoxy-2-methyl derivatives revealed the presence of m/z 188 in addition to [M+H]+ and the iminium species. This study served as an extension from previous work on isomeric 5-ethoxylated counterparts and confirmed the ability to differentiate between the two groups. The data provided here add to the existing body of literature and aim to serve both forensic and clinical communities.

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Analytical characterization of N,N‐diallyltryptamine (DALT) and 16 ring‐substituted derivatives

Brandt

Kavanagh

Dowling

et al. 2016

Drug Testing and Analysis

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Many N,N-dialkylated tryptamines show psychoactive properties in humans and the number of derivatives involved in multidisciplinary areas of research has grown over the last few decades. Whereas some derivatives form the basis of a range of medicinal products, others are predominantly encountered as recreational drugs, and in some cases, the areas of therapeutic and recreational use can overlap. In recent years, 5-methoxy-N,N-diallyltryptamine (5-MeO-DALT) has appeared as a new psychoactive substance (NPS) and ‘research chemical’ whereas 4-acetoxy-DALT and the ring-unsubstituted DALT have only been detected very recently. Strategies pursued in the authors’ laboratories included the preparation and biological evaluation of previously unreported N,N-diallyltryptamines (DALTs). This report describes the analytical characterization of seventeen DALTs. Fifteen DALTs were prepared by a microwave-accelerated Speeter and Anthony procedure following established procedures developed previously in the authors’ laboratories. In addition to DALT, the substances included in this study were 2-phenyl-, 4-acetoxy-, 4-hydroxy-, 4,5-ethylenedioxy-, 5-methyl-, 5-methoxy-, 5-methoxy-2-methyl-, 5-ethoxy-, 5-fluoro-, 5-fluoro-2-methyl-, 5-chloro-, 5-bromo-, 5,6-methylenedioxy-, 6-fluoro-, 7-methyl, and 7-ethyl-DALT, respectively. The DALTs were characterized by nuclear magnetic resonance spectroscopy (NMR), gas chromatography (GC) quadrupole and ion trap (EI/CI) mass spectrometry (MS), low and high mass accuracy MS/MS, ultraviolet diode array detection and GC solid-state infrared analysis, respectively. A comprehensive collection of spectral data was obtained that are provided to research communities who face the challenge of encountering newly emerging substances where analytical data are not available. These data are also relevant to researchers who might wish to explore the clinical and non-clinical uses of these substances.

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Microwave‐accelerated synthesis of psychoactive deuterated N,N‐dialkylated‐[α,α,β,β‐d₄]‐tryptamines

Cited by 15 publications

References 32 publications

Biotransformation and detectability of the new psychoactive substances N,N-diallyltryptamine (DALT) derivatives 5-fluoro-DALT, 7-methyl-DALT, and 5,6-methylenedioxy-DALT in urine using GC-MS, LC-MSn, and LC-HR-MS/MS

Biotransformation and detectability of the new psychoactive substances N,N-diallyltryptamine (DALT) derivatives 5-fluoro-DALT, 7-methyl-DALT, and 5,6-methylenedioxy-DALT in urine using GC-MS, LC-MSn, and LC-HR-MS/MS

Synthesis and characterization of 5‐methoxy‐2‐methyl‐N,N‐dialkylated tryptamines

Analytical characterization of N,N‐diallyltryptamine (DALT) and 16 ring‐substituted derivatives

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