Synthetic studies toward the marine alkaloid convolutindole A, a structurally remarkable derivative of the hallucinogen N,N-Dimethyltryptamine (DMT)
Karen Ichikawa, Jessica C. Neville, Yihan Yu, Jonathan Sperry
Tetrahedron Letters September 13, 2023 DOI: 10.1016/j.tetlet.2023.154756 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Topics | 5-MeO-DMT DMT |
| Citations | 3 |
| Key points | The authors report that a Fischer-reaction route to an advanced tryptamine intermediate failed, whereas an iterative C-H functionalisation strategy succeeded, converting 6-bromoindole through iridium-catalysed triborylation, selective protodeboronation, Chan-Evans-Lam and bromodeboronation steps, and reductive alkylation to give a tri-substituted tryptamine closely related to convolutindole A. They argue this showcases iridium-catalysed C-H borylation for making densely functionalised indoles. |
Abstract
Herein we report the results of a synthetic strategy toward the marine alkaloid convolutindole A, a structurally remarkable derivative of the hallucinogen N,N-dimethyltryptamine (DMT). While attempts to forge an advanced tryptamine intermediate using the Fischer reaction were unsuccessful, an iterative C-H functionalisation strategy proved more fruitful. Subjecting 6-bromoindole to an iridium-catalysed triborylation gave a 2,4,7-triborylindole, which underwent selective protodeboronation at C2. The resulting 4,7-diborylindole underwent selective Chan-Evans-Lam and bromodeboronation reactions at C7 and C4 respectively, affording 4,6-dibromo-7-methoxyindole. Installation of the tryptamine side chain was achieved by reductive alkylation (presumably via a β-methoxytryptamine intermediate) to give an advanced tri-substituted tryptamine closely related to convolutindole A, This work showcases the utility of the iridium-catalysed C-H borylation methodology to prepare densely functionalised indoles that would traditionally be accessed by heteroannulation, while providing an excellent foundation for our ongoing synthetic efforts toward convolutindole A.
Comparable studies
Other theoretical and historical papers on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| When the Endogenous Hallucinogenic Trace AmineN,N-Dimethyltryptamine Meets the Sigma-1 Receptor | 2009 | Theoretical or philosophical paper | |
| 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 | 2004 | Theoretical or philosophical paper | |
| Enlightening the "Spirit Molecule": Photomodulation of the 5-HT2A Receptor by a Light-Controllable N,N-Dimethyltryptamine Derivative. | 2022 | Theoretical or philosophical paper | |
| Conformational, spectroscopic and nonlinear optical properties of biologically active N,N-dimethyltryptamine molecule: a theoretical study. | 2014 | Theoretical or computational study | |
| Simple syntheses of lespedamine and 5-bromo-n,n-dimethyltryptamine based on 1-hydroxyindole chemistry | 1995 | Theoretical or philosophical paper |
Citations in the library
Cites 10
- A single inhalation of vapor from dried toad secretion containing 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a naturalistic setting is related to sustained enhancement of satisfaction with life, mindfulness-related capacities, and a decrement of psychopathological symptoms. Psychopharmacology April 13, 2019
- Psychedelic therapy for depressive symptoms: A systematic review and meta-analysis. Journal of Affective Disorders February 1, 2023
- The epidemiology of 5-methoxy- N, N-dimethyltryptamine (5-MeO-DMT) use: Benefits, consequences, patterns of use, subjective effects, and reasons for consumption. Journal of Psychopharmacology July 1, 2018
- Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment Psychopharmacology December 10, 2019
- The epidemiology of mescaline use: Pattern of use, motivations for consumption, and perceived consequences, benefits, and acute and enduring subjective effects. Journal of Psychopharmacology March 1, 2022
and 5 more in the library