Journal of Natural Products
May 30, 2003
Osamu Shirota, Wataru Hakamata, Yukihiro Goda
90 citations
Psilocin and psilocybin, the main hallucinogenic compounds in magic mushrooms, can be synthesized on a large scale without the need for chromatographic purification. The key step in producing psilocybin involves isolating a dibenzyl-protected intermediate as a zwitterionic derivative, which was fully characterized using two-dimensional NMR analyses.
Journal of Natural Products
February 20, 2020
Alexander M. Sherwood, Adam L. Halberstadt, Adam K. Klein et al.
79 citations
A new synthetic method allows access to tryptamine natural products found in psilocybin-producing mushrooms. Laboratory and animal experiments tested whether these compounds are psychoactive. In mice, the natural product baeocystin did not produce a head twitch response, a behavioral marker of psychedelic activity, even though its predicted breakdown product, norpsilocin, strongly activates the 5-HT2A receptor, which is associated with psychedelic effects. This suggests that baeocystin itself may not be psychedelic, despite its metabolite's activity.
Journal of Natural Products
December 1, 2006
Osamu Shirota, Kumi Nagamatsu, Setsuko Sekita
68 citations
Seven previously unknown neo-clerodane diterpenes—salvidivins A–D, salvinorins H and I, and divinatorin F—along with eight known compounds, were isolated from the hallucinogenic plant Salvia divinorum. Chemical structures of the new compounds were determined using two-dimensional nuclear magnetic resonance spectroscopy. These findings expand the known chemical diversity of this plant, which is of interest for its psychoactive properties.
Journal of Natural Products
September 20, 2017
Claudius Lenz, Jonas Wick, Dirk Hoffmeister
62 citations
A previously unreported natural compound, ω-N-methyl-4-hydroxytryptamine (norpsilocin), was identified in the fruiting bodies of the hallucinogenic mushroom Psilocybe cubensis. Its structure was determined using NMR spectroscopy and high-resolution mass spectrometry. Norpsilocin is likely the actual psychoactive agent released from its phosphate ester derivative, the known natural product baeocystin. The authors also developed a simple extraction method that avoids dephosphorylation, thereby preserving the natural metabolic profile of Psilocybe mushrooms for analysis.
Journal of Natural Products
January 1, 2006
Wayne W Harding, Matthew Schmidt, Kevin Tidgewell et al.
59 citations
Salvinorin A, a hallucinogen from the plant Salvia divinorum, is unique as the first non-nitrogenous compound known to bind to opioid receptors. To understand why it selectively targets kappa opioid receptors, researchers systematically altered its structure and tested the effects on receptor binding and activity. This work describes chemical transformations of salvinorin A, including a semisynthesis of salvinicins A and B. It also identifies compound 10a as the first neoclerodane diterpene with delta opioid antagonist activity, providing new tools for studying opioid receptor interactions.
Journal of Natural Products
May 1, 1981
Yutaka Koike, Kohko Wada, Genjiro Kusano et al.
45 citations
Psilocybin was isolated from the mushroom Psilocybe argentipes and its presence was determined in specimens of several mushroom species. The work details the chemical isolation and analytical methods used to identify and quantify the alkaloid in these fungi.
Journal of Natural Products
April 25, 2011
Anthony Lozama, Christopher W Cunningham, Michael J Caspers et al.
40 citations
New chemical methods using microwave heating enabled the first successful Diels-Alder cycloaddition reactions on the furan ring of salvinorin A, a neoclerodane diterpene natural product. This approach introduced electron-withdrawing groups and bulky aromatic rings at the C-12 position. Some of the resulting cycloadducts, specifically dimethyl- and diethylcarboxylate analogues, retained affinity and selectivity for kappa opioid receptors and acted as full agonists. However, converting these cycloadducts into planar phenyl ring systems reduced their receptor affinity. The work provides a novel strategy for rapidly exploring structure-activity relationships of furan-containing natural products.
Journal of Natural Products
April 23, 2010
Lukasz Kutrzeba, Xing-Cong Li, Yuanqing Ding et al.
23 citations
Fresh Salvia divinorum leaves yielded salvinorins E and D, which may be natural precursors to salvinorin A, a potent hallucinogen. During HPLC purification, salvinorin E spontaneously converted into a mixture with its regioisomer salvinorin D in a 3:5 ratio, observable by NMR. This isomerization occurs through a dynamic intramolecular transacetylation process.
Journal of Natural Products
September 27, 2013
Madan Kumar Paudel, Osamu Shirota, Kaori Sasaki-Tabata et al.
21 citations
A monoclonal antibody was created that recognizes salvinorin A, the main psychoactive compound in Salvia divinorum, and an indirect competitive enzyme-linked immunosorbent assay (icELISA) was developed to detect salvinorins. The assay's calibration range was 0.0195-0.625 μg/mL. Tests on plants from the mint family, including S. divinorum, showed the method is simple, precise, accurate, sensitive, and reliable for identifying the plant.
Journal of Natural Products
July 1, 1987
E. Ohenoja, J. Jokiranta, T. Mäkinen et al.
21 citations
Psilocybin and psilocin, the psychoactive compounds known from hallucinogenic mushrooms, were detected in several species of Finnish fungi. The study identified these alkaloids in specimens collected from various locations in Finland, confirming their presence in the region's fungal flora. The chemical analysis provided evidence for the occurrence of these substances, contributing to the understanding of their distribution in nature.
Journal of Natural Products
March 5, 2021
Janis Fricke, Alexander M. Sherwood, Adam L. Halberstadt et al.
18 citations
A novel analogue of psilocybin, 5-methylpsilocybin, was produced through a hybrid chemoenzymatic synthesis, combining chemical synthesis of 5-methylpsilocin with enzymatic phosphorylation using a purified kinase from Psilocybe cubensis. The product was isolated with high purity via solvent-antisolvent precipitation. In a mouse head-twitch response assay, 5-methylpsilocybin showed psychedelic-like activity more potent than dimethyltryptamine but less potent than psilocybin.
Journal of Natural Products
August 27, 2021
Camilla B Chan, Christian B M Poulie, Simon S Wismann et al.
13 citations
The term 'false peyote' is commonly applied to Lophophora diffusa, but several other unrelated cacti also share this name due to their resemblance to true peyote (Lophophora williamsii) or similar habitats. Over 40 alkaloids have been isolated from the Lophophora genus, yet only mescaline's pharmacological effects are well-studied. The major alkaloid in L. diffusa is pellotine, a tetrahydroisoquinoline briefly marketed as a sleeping aid in the early 1900s based on reports of its hypnotic properties. Pharmacological experiments on these alkaloids occurred around 1900, with chemical synthesis achieved decades later and biosynthetic pathways reported in the late 1960s. This review outlines the relationship of false peyotes to L. williamsii regarding alkaloid content, synthesis, and pharmacology.
Journal of Natural Products
July 1, 1986
W.-w. Ma, Xiaomo Jiang, R. Graham Cooks et al.
10 citations
Mescaline and related alkaloids were identified in eight additional cactus species using thin-layer chromatography (TLC) and tandem mass spectrometry (MS/MS). The work extends the known distribution of these compounds across the Cactaceae family.
Journal of Natural Products
March 1, 1982
Sunibhond Pummangura, Jerry L. Mclaughlin, R. C. Schifferdecker
10 citations
Grafting Trichocereus cacti does not cause mescaline to move from a mescaline-producing scion into a non-producing rootstock. The study tested for alkaloid translocation by grafting mescaline-containing Trichocereus tops onto non-alkaloid-producing rootstocks and analyzing the rootstock tissue. No mescaline was detected in the rootstocks, indicating that mescaline does not translocate across the graft union under the conditions tested. The finding suggests that mescaline remains localized in the tissues where it is synthesized.
Journal of Natural Products
June 23, 2023
Bruno González, Nicolás Veiga, Gonzalo Hernández et al.
7 citations
The iboga alkaloids, such as ibogaine and voacangine, are promising scaffolds for developing drugs to treat neuropsychiatric disorders. This work examines how these molecules react under oxidation with dioxygen, peroxo compounds, and iodine. The C16-carboxymethyl ester group in voacangine makes the molecule more stable toward oxidation than ibogaine, particularly in the indole ring, where 7-hydroxy- or 7-peroxy-indolenines form. However, the ester increases reactivity at the isoquinuclidinic nitrogen, leading to C3-oxidized products via regioselective iminium formation. Density functional theory calculations explain this differential reactivity. Additionally, NMR experiments and theoretical calculations revise the absolute stereochemistry at C7 in voacangine's 7-hydroxyindolenine to S, correcting earlier reports of R configuration.
Journal of Natural Products
March 22, 2024
Lucas Apolinário Chibli, Bruna Ribeiro de Lima, Ariadne Magalhães Carneiro et al.
4 citations
Alkaloid extraction traditionally relies on hazardous chemicals like HCl and CH₂Cl₂. This work tested whether that practice is justified by superior recovery. In three laboratories, alkaloids harmine, boldine, vincamine, and mescaline were extracted from four medicinal plants. Replacing HCl with citric acid maintained or improved extraction performance. Ethyl acetate could fully replace CH₂Cl₂ in three of four cases and partially in the fourth without loss. The alternative solvents tert-amyl methyl ether and n-butyl acetate also enhanced alkaloid extraction. These findings suggest natural products laboratories can adopt greener solvents and processes, aligning with current pharmaceutical industry practices.
Journal of Natural Products
July 28, 2017
Anil Yilmaz, Rachel Saylor Crowley, Alexander M. Sherwood et al.
Columbin, a natural compound from plants used in traditional medicine, was modified to create derivatives that might activate the kappa-opioid receptor (KOR), a target for conditions like anxiety, depression, and addiction. The derivatives showed slightly improved activity at the KOR compared to the original columbin, but neither the parent compound nor its derivatives were potent KOR ligands. This study is the first to test columbin at the KOR and explores chemical modifications that can be made to the columbin molecule.