Worldwide, there are plants known as psychoactive plants that naturally contain psychedelic active components. They have a high concentration of neuroprotective substances that can interact with the nervous system to produce psychedelic effects. Despite these plants' hazardous potential, recreational use of them is on the rise because of their psychoactive properties. Early neuroscience studies relied heavily on psychoactive plants and plant natural products (NPs), and both recreational and hazardous NPs have contributed significantly to the understanding of almost all neurotransmitter systems. Worldwide, there are many plants that contain psychoactive properties, and people have been using them for ages. Psychoactive plant compounds may significantly alter how people perceive the world.
1. J Org Chem. 2020 Mar 6;85(5):3949-3953. doi: 10.1021/acs.joc.9b03218. Epub 2020 Feb 12. Transition-Metal-Free Total Synthesis and Revision of the Absolute Configuration of Pipermethystine. Vázquez-Amaya LY(1), Quintero L(1), Rodrı Guez-Molina B(2), Sartillo-Piscil F(1). Author information: (1)Centro de Investigación de la Facultad de Ciencias Quı́micas, Benemérita Universidad Autónoma de Puebla (BUAP), 14 Sur Esq. San Claudio, Col. San Manuel, Puebla 72570, México. (2)Instituto de Quı́mica, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Ciudad de México 04510, México. Starting from 3-hydroxy piperidines, a novel transition-metal-free strategy to 5-hydroxy-5,6-dihydro-2(1H)pyridones is reported. This unprecedented approach, which provides a practical, economical, and ecofriendly alternative to either the classical ring-closing metathesis of N-homoallyl-unsaturated amides or the dehydrogenation of amides, occurs by means of a triple C-H functionalization of three unreactive piperidine sp3 carbons. The completion of the total synthesis revealed that the natural levo-isomer possesses the R absolute configuration, not S. DOI: 10.1021/acs.joc.9b03218 PMID: 31994875 2. Org Biomol Chem. 2017 Dec 19;16(1):77-88. doi: 10.1039/c7ob02700a. The direct and highly diastereoselective synthesis of 3,4-epoxy-2-piperidones. Application to the total synthesis and absolute configurational assignment of 3α,4α-epoxy-5β-pipermethystine. Osorio-Nieto U(1), Vázquez-Amaya LY, Höpfl H, Quintero L, Sartillo-Piscil F. Author information: (1)Centro de Investigación de la Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla (BUAP), 14 Sur Esq. San Claudio, Col. San Manuel, 72570, Puebla, México. fernando.sartillo@correo.buap.mx. The substrate-controlled asymmetric total synthesis and absolute configurational assignment of biologically active 3α,4α-epoxy-5β-pipermethystine, a minor component in the aerial parts of kava, has been achieved by featuring, as a key step, the environmentally friendly and direct synthesis of 2,3-epoxyamides from allyl amines. By using the chiron approach, first a carbohydrate-derived dehydropiperidine was prepared and subjected to a stereoselective tandem C-H/C[double bond, length as m-dash]C oxidation reaction. In this attempt, the required α,α-trans-epoxy-2-piperidone skeleton of the kava metabolite precursor was not achieved, although the tandem oxidation was highly stereoselective. However, starting from non-carbohydrate 3-hydroxy-4,5-dehydropiperidine, and using the same tandem oxidation, the target intermediate was obtained in high yield and complete unprecedented anti-stereoselectivity. Since the proposed mechanistic course of this tandem oxidation implies the transient formation of an α,β-unsaturated amide followed by the subsequent epoxidation reaction, this second approach supports the previously established biotransformation proposal of (-)-pipermethystine to (-)-3α,4α-epoxy-5β-pipermethystine. DOI: 10.1039/c7ob02700a PMID: 29192703 [Indexed for MEDLINE] 3. Phytother Res. 2012 Nov;26(11):1768-70. doi: 10.1002/ptr.4620. Epub 2012 Feb 8. Are mould hepatotoxins responsible for kava hepatotoxicity? Rowe A(1), Ramzan I. Author information: (1)Faculty of Pharmacy, University of Sydney, Sydney, New South Wales, Australia. Previous studies with kava components such as kavalactones, pipermethystine and flavokavain B have demonstrated hepatotoxicity from these constituents. Regardless, there has recently been speculation that adulterants or impurities such as the mould hepatotoxin aflatoxin are a more likely cause of kava hepatotoxicity, despite a paucity of supporting evidence. Although there is limited similarity between acute kava hepatotoxicity and acute aflatoxicosis, and background levels of aflatoxin have been detected in kava samples, unless epidemiological investigations can uncover direct evidence implicating mould hepatotoxins, it remains more likely that chemical constituents of kava are the cause of the hepatotoxicity from kava. Copyright © 2012 John Wiley & Sons, Ltd. DOI: 10.1002/ptr.4620 PMID: 22319018 [Indexed for MEDLINE] 4. Food Chem Toxicol. 2011 Oct;49(10):2503-16. doi: 10.1016/j.fct.2011.06.075. Epub 2011 Jul 3. Proposal for a kava quality standardization code. Teschke R(1), Lebot V. Author information: (1)Department of Internal Medicine II, Division of Gastroenterology and Hepatology, Klinikum Hanau, Teaching Hospital of the Goethe University of Frankfurt/Main, Germany. rolf.teschke@gmx.de Rare cases of hepatotoxicity emerged with the use of kava drugs and dietary supplements prepared from rhizomes and roots of the South Pacific plant kava (Piper methysticum). Their psychoactive, anxiolytic, relaxing, and recreational ingredients are the kavalactones kavain, dihydrokavain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin, but there is little evidence that these kavalactones or the non-kavalactones pipermethystine and flavokavain B are the culprits of the adverse hepatic reactions. It rather appears that poor quality of the kava material was responsible for the liver toxicity. Analysis of existing kava quality standardizations with focus on chemical, agricultural, manufacturing, nutritional, regulatory, and legislation backgrounds showed major shortcomings that could easily explain quality problems. We therefore suggest a uniform, internationally accepted device for kava quality standardizations that are in the interest of the consumers because of safety reasons and will meet the expectations of kava farmers, pharmaceutical manufacturers, regulators of agencies, and legislators. The initial step resides in the establishment of Pan-Pacific kava quality legislation as an important part of the proposed Kava Quality Standardization Code. In conclusion, a sophisticated approach to establish kava quality standardizations is needed for safe human use of kava as relaxing traditional beverages, the anxiolytic drugs, and recreational dietary supplements. Copyright © 2011 Elsevier Ltd. All rights reserved. DOI: 10.1016/j.fct.2011.06.075 PMID: 21756963 [Indexed for MEDLINE] 5. Chem Res Toxicol. 2011 Jul 18;24(7):992-1002. doi: 10.1021/tx100412m. Epub 2011 May 3. Constituents in kava extracts potentially involved in hepatotoxicity: a review. Olsen LR(1), Grillo MP, Skonberg C. Author information: (1)Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Denmark. lo@entomopharm.dk Aqueous kava root preparations have been consumed in the South Pacific as an apparently safe ceremonial and cultural drink for centuries. However, several reports of hepatotoxicity have been linked to the consumption of kava extracts in Western countries, where mainly ethanolic or acetonic extracts are used. The mechanism of toxicity has not been established, although several theories have been put forward. The composition of the major constituents, the kava lactones, varies according to preparation method and species of kava plant, and thus, the toxicity of the individual lactones has been tested in order to establish whether a single lactone or a certain composition of lactones may be responsible for the increased prevalence of kava-induced hepatotoxicity in Western countries. However, no such conclusion has been made on the basis of current data. Inhibition or induction of the major metabolizing enzymes, which might result in drug interactions, has also gained attention, but ambiguous results have been reported. On the basis of the chemical structures of kava constituents, the formation of reactive metabolites has also been suggested as an explanation of toxicity. Furthermore, skin rash is a side effect in kava consumers, which may be indicative of the formation of reactive metabolites and covalent binding to skin proteins leading to immune-mediated responses. Reactive metabolites of kava lactones have been identified in vitro as glutathione (GSH) conjugates and in vivo as mercapturates excreted in urine. Addition of GSH to kava extracts has been shown to reduce cytotoxicity in vitro, which suggests the presence of inherently reactive constituents. Only a few studies have investigated the toxicity of the minor constituents present in kava extract, such as pipermethystine and the flavokavains, where some have been shown to display higher in vitro cytotoxicity than the lactones. To date, there remains no indisputable reason for the increased prevalence of kava-induced hepatotoxicity in Western countries. © 2011 American Chemical Society DOI: 10.1021/tx100412m PMID: 21506562 [Indexed for MEDLINE]