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Tetrahydroisoquinoline alkaloids of the Mexican columnar cactus Pachycereus Weberi
Abstract
Eight tetrahydroisoquinoline alkaloids have been crystallized and identified from the nonphenolic and phenolic extracts of the giant Mexican cereoid cactus, Pachycereus weberi (Coult.) Br. and R. The identities were established as 5,6,7-trimethoxy-1,2,3,4- tetrahydroisoquinoline (nortehuanine) 1; 7,8-dimethoxy-1,2,3,4-tetrahydroisoquinoline (lemaireocercine) 2; 7-methoxy-1, 2,3,4-tetrahydroisoquinoline (weberidine) 3; 5,6,7,8-tetramethoxy-1,2,3,4-tetrahydroisoquinoline (weberine) 4; 6,7- dimethoxy-1,2,3,4-tetrahydroisoquinoline (heliamine) 5; 2-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (N- methylheliamine or oxymethyl-corypalline) 6; 2-methyl-5,6,7-trimethoxy-1,2,3,4-tetrahydroisoquinoline (tehuanine) 7; and 1,2-dimethyl-6,7-dimethoxy-8-hydroxy-1,2,3,4-tetrahydroisoquinoline (pellotine) 8. Compounds 1- 4 have not been identified previously as natural compounds, while compounds 5-8 are previously known cactus alkaloids.
... Currently there is no definite explanation of the psychoactive effect of heliamine found in cacti Backbergia militaris and Carnegiea gigantea, and extracted from fresh Berberis leaves (Berberis integerrima) [5][6][7][8][9]. However, heliamine is known to interact with adrenergic receptors. ...
... We have studied the possibility of heliamine identification by means of infrared radiation spectroscopy ( fig. 3). The IR spectrum shown in fig. 3 allows to make a conclusion that the disposition of the main absorption bands and their relative abundance ( max, сm -1 : 2909, 2762, 1612, 1518, 1261, 1228.5, 1154, 1015, 894, 735) follows the discussed heliamine structure and does not contradict the data submitted in the papers [5,9]. Therefore, the received results allow to come to the conclusion that we have determined the chemical structure of the new "designer drug " -6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline. ...
The results of comprehensive research «designer drugs» – 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline using thin layer chromatography, gas chromatography/mass-spectrometry with electronic and chemical ionization, NMR- and IR-spectroscopy are presented. To identify 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline objects forensic examinations suggested to use mass-spectrometry and gas chromatography retention parameters, and its IR-spectrum.
The ink used by Volta in his scripts appears to be a very complex mixture. Our analysis of the eluates from the EVA diskettes (via GCXGC/TOFMS) has revealed the presence of more than 1800 unique metabolites. The ink thus appears to be a very complex combination of different ingredients, mainly consisting of tannins, vegetable oils and resins together with root and wood dyes. In particular, the presence of hydroxy and dihydroxyanthraquinones, as well as natural quinoids, evidenced the use of madder dyes from Rubiaceae as an important component of this ink. Natural quinoids, based on a 9, 10-anthraquinone skeleton, hydroquinone and anthrone derivatives, and even the specific marker of alizarin, indicate the use of the Rubia tinctorum. Additionally, the presence of several signals of fatty acids, saturated and unsaturated mono and dicarboxylic acids, as well as of the typical signals of Pinaceae resins substantiated the use of a vegetable oil and colophony. Several signals of cyclic monosaccharides suggested also the use of natural gum (Acacia Senegal also known as Arabic gum). It is known that Arabic gum, as well as linseed oil, were often employed as thickeners to increase the viscosity of the ink and to protect it from excess absorption of atmospheric oxygen. Curiously, we also found characteristic signals from alkaloids such as Dioncophyllin A and B, typical metabolites from tropical/exotic plants such as Triphyophyllum, Habropeltatum and Dioncophyllum. To our reckoning such an extensive array of ingredients in inks adopted over millennia has never been reported. © Académie des sciences, Paris and the authors, 2021. Some rights reserved.
This chapter focuses on isoquinoline alkaloids that do not contain additional cyclic structures except a methylenedioxy substituent. The chapter also discusses 1 - and 4-phenylsubstituted and N-benzyl-substituted tetrahydroisoquinolines because of their close structural relationship. These results strongly suggest that simple tetrahydroisoquinolines, such as anhalamine and anhalonidine are biogenetically derived from 3-demethylmescaline, which condenses with glyoxylic or pyruvic acid to give peyoxylic or peyoruvic acid. These amino acids undergo oxidative decarboxylation to supply 3,4-dihydroisoquinolines, which are then stereospecifically reduced to the tetrahydroisoquinolines. Simple tetrahydroisoquinolines show both, central and peripheral pharmacological effects. They may have central nervous system depressant or stimulant and convulsant properties. They can also cause vasopressor or depressor actions, various effects on the smooth muscle, and lipid-mobilizing activity. Some alkaloids are insecticidal. The alkaloids of the sinita cactus Lophocereus schottii are toxic to most Drosophila species except D.pachea, which is the only species that breeds in old stems of the cactus.
This chapter the procedures used in crystal-structure analysis, provides a guide to the evaluation of the published results, provides examples of the different types of information available from diffraction experiments, and describes a few alkaloids with unusual structural features. The various kinds of information that are immediately derivable from a crystal-structure analysis by X-ray diffraction and their applications to alkaloid molecules are discussed. From unequivocally providing the structural formula, stereochemistry, and absolute configuration of an alkaloid of unknown formula to establishing the spatial arrangement of the atoms, particularly the disposition of the atoms that are the reactive centers or that provide a steric hindrance to reaction, crystal-structure analyses are extremely useful and often indispensable. A classic procedure in the chemical study of alkaloids includes extraction from a plant or animal source, chemical isolation and purification of the active principal, elucidation of the molecular formula by means of chemical degradation, mass spectrometry, infrared, ultraviolet, and nuclear magnetic resonance analyses, and laboratory synthesis of the product.
The present review describes research on novel natural isoquinoline alkaloids and their N-oxides isolated from different plant species. More than 200 biological active compounds have been showed confirmed antimicrobial, antibacterial, antitumor, and other activities. The structures, origins, and reported biological activities of a selection of isoquinoline N-oxides alkaloids are reviewed. With the computer program PASS some additional SAR (structure–activity relationship) activities are also predicted, which point toward new possible applications of these compounds. This review emphasizes the role of isoquinoline N-oxides alkaloids as an important source of leads for drug discovery.
A synthesis of 1,2,3,4-tetrahydroisoquinolines (TIQs) (23) with one and two methoxyl groups at various positions of the benzene ring was achieved via the intramolecular cyclization of N-(aryl)methyl-2- (phenylsulfinyl)ethylamines (9) using the Pummerer reaction as a key step. The reaction was carried out by using trifluoroacetic anhydride (TFAA) (method A) or TFAA-BF 3 · Et 2O (method B). The cyclization to 4-SPhTIQs (11) proceeded effectively when the reaction center at the benzene ring was electronically activated by a methoxyl group. In the reaction of the sulfoxide (9e) having two OMe groups at ortho- and para-positions a different cyclization reaction leading to a benzothiazepine (12) was observed, indicating that the high nucleophilicity of the benzene ring caused the unexpected reaction prior to the cyclization to 4-SPhTIQ (11e). The route starting from methoxylated benzaldehydes (5) was proved to provide an efficient and convenient method of TIQ synthesis which should be complementary to the well known Pictet-Spengler method.
Wild Cardon cactus seeds were inoculated with Azospirillum brasilense strains Cd and Sp-245 to improve seed germination and seedling growth parame- ters. Differential germination responses were related to the bacterial strain. A. brasilense Cd (the type strain for the species A. brasilense) significantly decreased seed germination. A. brasilense Sp245 (a known beneficial bacteria for cereal plants) significantly increased the germination of the seedlings at the same inoculum concentration. Both bacterial strains improved several plant growth parameters related to seedling survivability (height, diameter, volume and the volume/surface ratio) and decreased the aging process of the seedling spines. Both strains of A. brasilense survived in the cactus rhizosphere for about 300 days after seed inoculation. This study adds further evidence that A. brasilense should be considered as a non-specific beneficial bacteria and we propose the inoculation of Cardon cactus seeds as a possible means of enhancing seedling growth in nurseries.
Pummerer reaction of the sulfoxides 5 of N-acyl-N-(aryl)methyl-2- (phenylthio)ethylamines (4) on treatment with trifluoroacetic anhydride (TFAA) effectively caused intramolecular cyclization under a mild condition to give N-acyl-4-phenylthin-1,2,3,4-tetrahydroisoquinolines (TIQs) (7). The reaction of the N-formyl sulfoxide 5c without a methoxy group in the benzene ring using a formyl group for N-protection is particularly efficient. Treatment of the N-formyl sulfoxide 5f with TFAA did not give away TIQ, but a sequential treatment using TFAA and BF 3·Et 2O afforded N-formyl-4- phenylthio-TIQ (7f) in quantitative yield. The efficiency of this method or preparing TIQs was demonstrated in the synthesis of 1,4-dideuterio-TQ (10D) and its N-methyl derivative (11D).
13C NMR resonances of 15 simple tetrahydroisoquinolines have been assigned on the basis of chemical shift theory, 13C-1H coupling constants
Pummerer reaction of N-trimethoxybenzyl-N-[2- (phenylsulfinyl)ethyl]formamides (7) gave N-formyl-1,2,3,4-tetrahydro-4- phenyl-sulfanylisoquinolines (9) which were converted into trimethoxylated 1,2,3,4-tetrahydroisoquinoline alkaloids in the family of Cactaceae, formylanhalinine (10a), nortehaunine (12a), anhalinine (12b), and tehaunine (13a).
The reaction of the N-acylated enamino ketones 4a–d with trifluoroacetic acid, TMS triflate, or Lewis acids leads to the 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines 5a–d in 84 to 94% yield. The enamino ketones 4f–i can only be cyclized with trifluoromethanesulfonic acid to the 1,2,3,4-tetrahydroisoquinolines 5f–i in 75–84% yield. For the synthesis of 5e from the enamino ketone 4e carrying the benzyloxycarbonyl group TMS triflate is the best mediator (93%). The trichloromethylcarbonyl group in 5 can easily be transformed into a methoxycarbonyl group by treatment with K2CO3 in methanol to give 6 in 83–90% yield.
The giant columnar cardon cactus (Pachycereus pringlei) appears to have an ailment(s) that is destroying a large number of plants. The causal agent(s), whether biotic or abiotic, has yet to be determined. Two forms of symptom development have been recorded. The first is a circular tissue decay on a branch leading to death of the growing tip. In this case, the dead portion detaches and forms a "flat top" on the living part (hence the proposed name for this phenomenon). Progressive degeneration and death of the plant ensue. The second form is an initial circular crack on the branch without decay. Later, the green branch above the crack detaches, creating the characteristic flat top. A third type of degeneration was also observed: fatal bleaching. The time period between symptoms is unknown. It primarily affects mature, more than 100-year-old plants, but relatively young plants are also affected. Thirty-one field surveys covering the entire state of Baja California Sur found four major and three smaller centers of flat top decay. We believe that flat top decay syndrome of the cardon cacti in Baja California is common and widespread.
Cited By (since 1996):24, Export Date: 24 April 2013, Source: Scopus, CODEN: TETRA, :doi 10.1016/j.tet.2004.08.033, Language of Original Document: English, Correspondence Address: Inst. Quim. Organ. Sintesis-IQUIOS, Universidad Nacional de Rosario, Suipacha 531, S2002LRK Rosario, A.Argentina; email: tkaufman@fbioyf.unr.edu.ar, : Chemicals/CAScarnegine, 490-53-9, 55056-94-5; imine, 13774-92-0; methyl iodide, 74-88-4; salsolidine, 493-48-1; sulfoxide, 120-62-7, References: Shamma, M., Moniot, J.L., (1978) Isoquinoline Alkaloids Research, 1972-1977, , Plenum: New York;
Various simple tetrahydroisoquinoline alkaloids (Ia, b, c, IIa and IIIa, b, c) have been synthesized by the reaction of appropriate arylethylamines with paraformaldehyde or formaldehyde in formic acid.
In a reinvestigation of the alkaloids of the title cactus species, two trace alkaloids were isolated: heliamine (6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline) (0.007% yield), previously known from other cereoid cacti, and 1,2-dehydrosalsolidine (1-methyl-6,7-dimethoxy-3,4-dihydroisoquinoline) (0.006% yield), a novel fluorescent, tertiary amine. Mikes (ms/ms) analysis of the plant material and extracts suggests that the new alkaloid is not an extraction artifact. This is the first isolation of a dihydroisoquinoline from the Cactaceae; such compounds are speculated to be precursors of the more common tetrahydroisoquinolines; the use of ms/ms to detect traces of potential biosynthetic intermediates is emphasized.
Lemairin (1),β-[4-(β-D-glucopyranosyloxy)-3-hydroxyphenyl]-ethanol) has been crystallized from the phenolic fraction of an ethanol extract of the title plant. This novel glucoside may be involved in the rapid darkening characteristic of damaged tissues in certain cactus species.
The electron impact mass spectral fragmentation of a series of 3-substituted-l,2,3,4-tetrahydroisoquinolines are reported. The principal fragmentation modes of these compounds comply with the main generalizations reached earlier with simpler systems. Complete aromatizations to form the isoquinolinium ion are observed only for compounds 5 and 7 and no retro-Diels-Alder cleavage is observed when R1 is a benzyl group.
Tehuanine N-oxide was isolated from Pachycereus pringlei, and deglucopterocereine N-oxide was isolated from Pterocereus gaumeri. These
A new approach to the synthesis of 7,8-dioxygenated tetrahydroisoquinoline alkaloids based on the phot-Fries rearrangement of esters derived from 3-hydroxy-4-methoxy phenylacetonitrile is reported. The procedure was applied to the synthesis of the alkaloid Arizonine and 1-benzyl tetrahydroisoquinoline precursor of cularine and 1,2-berbine alkaloids.
The occurrence of tetrahydroisoquinolines (TIQ’s) and β-carbolines (BC’s) in mammals under physiological conditions is discussed con-troversially. A reason for some scepticism might be that the determination of TIQ’s and BC’s requires more sensitive methods than the measurement of known neurotransmitters like noradrenaline (NA), dopamine (DA), and 5-hydroxytryptamine (5-HT) which serve as precursors. The concentrations of the transmitters in the central nervous system (CNS) of mammals exceed those of most TIQ’s and BC’s by the factor 1000 at least. Furthermore, artefactual admixtures due to contaminations of organic solvents either with the trace amines themselves or with their precursors have to be prevented during the work up procedure. Finally some foodstuff contains TIQ’s and BC’s which gives rise to question endogenous formation by mammals.
Twenty new alkaloids, of which 13 are new natural products, have been discovered in Pachycereus weberi by tandem mass spectrometry using a mass-analyzed ion kinetic energy spectrometer. These observations have been confirmed by chromatography and, in many cases, by simple synthetic interconversions from known alkaloids. Particularly significant to the discovery of several alkaloids having the same molecular formula. Isomer distinctions such as these, which are difficult to make on pure compounds by mass spectrometry, were made by utilizing daughter spectra recorded successively during the evaporation of the material from the probe and/or from spectra recorded on different types of plant extracts. This study suggests that many natural materials may contain trace amounts of compounds of potential biomedical or synthetic interest and, in particular, that the number of known alkaloids might be greatly increased by experiments of this type.
Tandem mass spectrometry, applied to simple extracts of Backebergia militaris, indicated the presence of a number of new alkaloids, including fully aromatic oxygenated isoquinolines, their di- and tetra-hydro analogs, and beta-phenethylamines. These conclusions were supported by separation using radial tlc and comparison with authentic compounds. Traces of seven alkaloids new to this cactus species were identified; four (3,4,8,11) were known previously from other cacti. Three novel cactus alkaloids were identified and confirmed by synthesis as 7,8-dimethoxy-3,4-dihydroisoquinoline (12, dehydrolemaireocereine), 6,7-dimethoxyisoquinoline (13, backebergine), and 7,8-dimethoxyisoquinoline (14, isobackebergine). The last two compounds are the first simple, fully aromatic, isoquinoline alkaloids to be reported from the Cactaceae. The sensitivity of this approach to new alkaloid discovery is emphasized; the entire project consumed only 10 g of dried plant material.
The tetrahydroisoquinoline alkaloids tepenine, tehaunine, and gigantine (as its methyl ether) have been synthesized; a revised structure of gigantine is offered.
Tyramine, N-methyltyramine, hordenine, and candicine have been identified by TLC as new alkaloids of the peyote cactus, L. williamsii. Hordenine and N-methyltyramine were isolated in crystalline form bringing the number of alkaloids isolated from peyote to thirteen.
Seven crystalline alkaloids have been isolated and identified from extracts of a Mexican "peyote" cactus, Dolichothele longimamma (DC.) Br. and R. Five of these are new alkaloids: N-methyl-β-hydroxy-4-methoxy-β-phenethylamine (longimammine or 4-O-methylsynephrine), 6-hydroxy-2-methyl-1,2,3,4-tetrahydroisoquinoline (longimammosine), 8-hydroxy-2-methyl-1,2,3,4-tetrahydroisoquinoline (longimammidine), 6-methoxy-1,2,3,4-tetrahydroisoquinoline (longimammatine), and 4,8-dihydroxy-2-methyl-1,2,3,4-tetrahydroisoquinoline (longimammamine). Although these compounds have all previously been synthesized, a new and convenient route is described for the syntheses of longimammidine and longimammosine. The known cactus alkaloids, (-)-normacromerine and (±)-synephrine, were also found in this species.
Stem transections of 64 arborescent and fruticose species of columnar cacti were studied to evaluate present systematic treatments of Mexican taxa. Species examined included not only most Mexican taxa, primarily of tribe Pachycereeae, but also related and unrelated taxa from the West Indies and Central and South America. A review of stem biochemical literature on Mexican columnar cacti showed that triterpenes and alkaloids are mutually exclusive, except in Lophocereus. In taxa with abundant stem triterpenes all species of Stenocereus have silica bodies in the skin, whereas species of Escontria, Myrtillocactus, and Polaskia lack silica bodies. In species which have alkaloids, crystals are generally lacking, but in species closely related to alkaloid-bearing taxa the skin contains abundant calcium oxalate crystals in an unusual pattern. When these and other data on vegetative and reproductive morphology of Pachycereeae are used, two subtribes, Pachycereinae and Stenocereinae, can be clearly defined. Pachycereinae includes taxa that lack funicular pigment cells at anthesis but have either abundant alkaloids or calcium oxalate crystals in the skin, whereas Stenocereinae includes taxa that have abundant triterpenes and funicular pigment cells at anthesis, many which also have silica bodies. Five new combinations are proposed for Mexican species that were assigned to Heliabravoa, and Machaerocereus and Rathbunia, which are submerged into Polaskia and Stenocereus, respectively. Based on a proposed phylogeny of Pachycereeae, evolutionary trends of vegetative and reproductive features are analyzed. The probable center of early radiation of Pachycereeae is southern Mexico, and geographical isolation has apparently encouraged allopatric speciation of numerous phylads. The assemblage of columnar cacti in the Sonoran Desert is composed of highly specialized species of at least seven distinct phylads, and species are closely related to southern forms and not to sympatric species.
A detailed study has shown that all possible aromatic dimethoxy-substituted 3,4-dihydroisoquinolines can be partially O-demethylated by controlled acid hydrolysis. Based on the structure elucidation of the monophenols thus obtained, it was established that preferential cleavage occurs at the 5-methoxyl with the 5,6- and 5,8-isomers 1 and 3, respectively, at the 6-methoxyl with the 6,8-isomer 4, at the 7-methoxyl with the 5,7-isomer 5, and at the 8-methoxyl with the 7,8-isomer 2.
A reaction scheme has been worked out which allows the synthesis of substituted N-methyl-1,2,3,4-tetrahydroisoquinolines from substituted benzaldehydes in high over-all yields. Using this method, two alkaloids, corypalline and hydrohydrastinine, have been prepared. Secondly, a method has been devised for preparing N-substituted 1,2,3,4-tetrahydroisoquinolines where the alkyl group is varied from methyl to t-butyl. The method uses glycidol followed by periodate oxidation to produce carbons 3 and 4 of the isoquinoline.
A new synthesis of 1,2,3,4-tetrahydroisoquinolines has been elaborated. It is based upon the reductive cyclization of N-benzylaminoacetaldehydes and is similar to the Fischer modification of the Pomeranz-Fritsch synthesis. The reactions of N-benzylaminoacetaldehydes with dilute acid were studied.
The dried branches of Trichocereus terscheckii (Parmentier) Britton & Rose contain 0.25 to 1.2% alkaloids. From this source trichocereine, a new vegetable base, and the already known mezcaline have been isolated and characterized. The ratio of trichocereine to mezcaline is 5:1. The chemical structure of trichocereine has been shown to be N-dimethylmezcaline by degradation, and its synthesis has been achieved by allowing 3,4,5-trimethoxy-β-phenylethyl chloride to react with dimethylamine.
The four known Cactus alkaloids anhalamine (II), anhalidine (III), rac. anhalonidine (IV) and rac pellotine (V) have been synthesized starting from mescaline (I) by new and simple procedures.
The traditional pharmacopoeia of the Seri Indians of Sonora, Mexico, involves approximately 95 species of plants in 80 genera,
15 animal species, and one kind of clay. In contrast only 75 species of plants were utilized for food. Medicinal teas are
prepared from 63 plant species. Plants with aromatic foliage are especially esteemed. The predilection for watery preparations
seems to be related to the commonplace water deficit in a very hot and arid environment.
Although a shaman was frequently involved in curing sickness, he generally did not administer medicines. For the most part,
traditional Seri medicine has been a highly individual affair. The few mixtures are relatively simple preparations. The absence
of complicated formulae encourages self-administered medicines and the information can readily diffuse through the culture.
Because it is an individual-oriented and non-professionally administered pharmacopoeia, each individual may not know every
remedy. To the Seri, origin and use of their various remedies appear to be highly pragmatic, often based on trial and error,
i.e., it is effective.
The saguaro,Carnegiea gigantea, is a tall cactus native to the desert area of southern Arizona and northern Sonora, Mexico. It has been used for centuries
among the Indians of the region as a source of food and drink, as well as for a wide variety of other purposes. The cactus
has taken a great place in the life of the Indians, most notably the Papago, who still collect the fruit and make a wine for
ceremonial purposes from it. Several botanical, ethnobotanical and phytochemical studies have been made on the cactus, whose
flower is the State Flower of Arizona.
A total of ten alkaloids have been identified in extracts of a Mexican cactus, Dolichothele uberiformis (Zucc.) Br. and R. The data provide documentation for the presence of (--)-synephrine, (--)-longimammine, N-methyl-3,4-dimethoxy-beta-phenethylamine, N-methyl-4-methoxy-beta-phenethylamine, (--y-normacromerine, N-methyltryramine, hordenine, longimammatine, and the first reported isolation of (--)-N,N-dimethyl-beta-hydroxy-beta-phenethylamine (ubine) from a natural source. Spectral data support the identification of another new alkaloid (uberine) as 5-methoxy-7-hydroxy-2-methyl-1,2,3,4-tetrahydroisoquinoline.
Three Mexican populations of peyote cactus have been analyzed for alkaloids by means of TLC. The southern population has a distinctly different chemical composition than the other two. This result supports the designation of the southern population as a different species. Unlike the other alkaloids investigated, hordenine occurs only in the roots of peyote.
Hordenine, anhalidine, pellotine, 3-demethyltrichocereine, mescaline, dimethoxy-beta-phenethylamine, and the N-monomethyl derivatives of mescaline d 3,4-dimethoxy-beta-phenethylamine have been isolated or identified, or both, in caloid extracts of a Mexican "peyote" cactus, Pelecyphora aselliformis tenberg. This is the first report of the occurrence of some of these alkaloids, including mescaline, in a North American cactus other than Lophophora.
- Spath