Alkaloid From Wikipedia, the free encyclopedia This article is about the chemical compounds alkaloids. For the pharmaceutical the pharmaceutical company in the Republic of Macedonia, Macedonia, see Alkaloid (company). (company).
Papaver The first individual alkaloid, morphine morphine,, was isolated in 1804 from poppy from poppy ( Papaver [1] somniferum). Alkaloids are a group of naturally occurring chemical
compounds which mostly contain basic nitrogen atoms. This group also includes some related compounds with neutral[2] and even weakly acidic acidic properties. properties.[3] Also some synthetic compounds of similar structure are attributed to alkaloids.[4] In addition to carbon carbon,, hydrogen and nitrogen nitrogen,, alkaloids may also contain oxygen oxygen,, sulfur sulfur and and more rarely other elements such as chlorine chlorine,, bromine and [5] phosphorus.. phosphorus Alkaloids are produced by a large variety of organisms, including bacteria including bacteria,, fungi fungi,, plants plants,, and animals and are part of the group of natural of natural products (also called secondary metabolites). metabolites ). Many alkaloids can be purified from crude extracts by acid-base extraction. extraction. Many alkaloids are toxic to other organisms. They often have pharmacological have pharmacological effects and are used as medications medications,, as recreational drugs, drugs, or in entheogenic rituals. Examples are the local anesthetic and stimulant stimulant,, cocaine cocaine;; the stimulant, caffeine caffeine;; nicotine nicotine;; the analgesic,, morphine analgesic morphine;; the antibacterial, berberine antibacterial, berberine;; the anticancer compound, vincrinstine vincrinstine;; the antihypertension agent, resepine resepine;; the cholinomimeric, galatamine galatamine;; the spasmolysis agent, atropine atropine;; the vasodilator, vincamine vincamine;; the anti-arhythmia compound, quinidine quinidine;; the anti-asthma therapeutic, ephedrine ephedrine;; and the antimalarial drug, drug, quinine quinine.. Although alkaloids act on a diversity of metabolic systems in humans and other animals, they almost uniformly invoke a bitter a bitter taste. taste.[6] The boundary between alkaloids and other nitrogen-containing natural compounds is not clear-cut.[7] Compounds like amino acid peptides acid peptides,, proteins proteins,, nucleotides nucleotides,, nucleic acid, acid, [2] amines and antibiotics are usually not called alkaloids. Natural compounds containing nitrogen in the exocyclic position (mescaline (mescaline,, serotonin serotonin,, dopamine dopamine,, etc.) are usually [8] attributed to amines rather than alkaloids. Some authors, however, consider alkaloids a [9][10][ [10][11] 11] special case of amines.[9]
Contents [hide hide]]
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1 Naming 2 His Histo tory ry 3 Clas Classif sificat ication ion 4 Pro Proper perties ties 5 Distribution in nature 6 Extr Extract action ion 7 Bio Biosyn synthes thesis is 7.1 Synthesis of Schiff bases 7.2 Mannich react reaction ion 8 Dime Dimerr alk alkalo aloids ids 9 The biologi biological cal role 10 App Applica lication tionss 10.11 In medi 10. medicin cinee 10.2 In agricu agriculture lture 10.3 Use as psycho psychoactive active drugs 11 Se Seee als alsoo 12 Notes 13 Ref Refere erence ncess
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14 Bib Bibliog liograp raphy hy
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[edit edit]] Naming
The article which introduced the concept of "alkaloid".
The name "alkaloids" (German (German:: Alkaloide) was introduced in 1819 by the German Latin:: alkali (which, in chemist Carl F.W. Meissner,[12] and is derived from late Latin root Latin turn, comes from the Arabic al qualja - "ashes of plants") and the suffix Greek : ειδοσ "like".[nb 1] However, the term came into wide use only after the publication of a review article by O. Jacobsen in the chemical dictionary of Albert of Albert Ladenburg in the 1880s.[13] There is no unique method of naming alkaloids.[14] Many individual names are formed by adding the suffix "-ine" to the species or generic alkaloids.[15] For example, atropine is isolated from the plant Atropa belladonna, belladonna, strychnine is obtained from the seed of [5] Strychnine tree. tree. If several alkaloids are extracted from one plant then their names often contain suffixes "-idine", "-anine", "-aline", "-inine", etc. There are also at least 86 alkaloids containing the root "vin" (extracted from the Vinca plant).[16]
[edit edit]] History Alkaloid-containing plants were used by humans since ancient times for therapeutic and recreational purposes. For example, medicinal plants have been known in the Mesopotamia at least around 2000 BC.[17] The Odyssey of Homer of Homer referred referred to a gift given to Helen by the Egyptian queen, a drug bringing oblivion. It is believed that the gift was an opium-containing drug.[18] A Chinese book on houseplants written in 1st-3rd centuries BC mentioned a medical use of Ephedra of Ephedra and opium poppies. poppies.[19] Also, coca leaves were used by South American Indians since ancient times.[20] Extracts from plants containing toxic alkaloids, such as aconitine and tubocurarine tubocurarine,, were [17] used since antiquity for poisoning arrows.
Friedrich Sertürner , the German chemist who first isolated morphine from opium opium.. Studies of alkaloids began in the 19th century. In 1804, the German chemist Friedrich Sertürner isolated Sertürner isolated from opium a "soporific principle" (Latin (Latin:: principium somniferum), which he called "morphium" in honor of Morpheus of Morpheus,, the Greek Greek god god of dreams; in German and some other Central-European languages, this is still the name of the drug. The term "morphine", used in English and French, was given by the French physicist Joseph Louis Gay-Lussac). Gay-Lussac ).
A significant contribution to the chemistry c hemistry of alkaloids in the early years of its development was made by the French researchers Pierre Joseph Pelletier and Pelletier and Joseph Bienaimé Caventou who discovered quinine (1820) and strychnine (1818). Several other alkaloids were discovered around that time, including xanthine (1817), atropine (1819), caffeine (1820), coniine (1827), nicotine (1828), colchicine (1833), sparteine (1851) and cocaine (1860).[21] The first complete synthesis of an alkaloid was achieved in 1886 by the German chemist Albert Ladenburg. Ladenburg. He produced coniine by reacting 2-methylpyridine with acetaldehyde [22][23] [23] and reducing the resulting 2-propenyl pyridine with sodium sodium..[22] The development of the chemistry of alkaloids was accelerated by the emergence of spectroscopic of spectroscopic and chromatographic methods in the 20th century, so that by 2008 more than 12,000 alkaloids had been identified.[24]
[edit edit]] Classification
Bufotenin, a poison from some toads, contains an indole core and is produced in living Bufotenin, organisms from the amino acid tryptophan tryptophan..
The nicotine molecule contains both pyridine both pyridine (left) and pyrrolidine and pyrrolidine rings (right). Compared with most other classes of natural compounds, alkaloids are characterized by a great structural diversity and there is no uniform classification of alkaloids.[25] Historically, first classification methods combined alkaloids by the common natural source, e.g., a certain type of plants. This classification was justified by the lack of [5][26] 26] knowledge about the chemical structure of alkaloids and is now considered obsolete. obsolete.[5][ More recent classifications are based on similarity of the carbon skeleton (e.g., indole indole,, isoquinoline and pyridine and pyridine-like) -like) or biogenetic precursor (ornithine (ornithine,, lysine lysine,, tyrosine tyrosine,, [5] tryptophan,, etc.). However, they require compromises in borderline cases;[25] for tryptophan example, nicotine contains a pyridine fragment from nicotinamide and pyrrolidine and pyrrolidine part [27] [28] from ornithine and therefore can be assigned to both classes.
Alkaloids are often divided into the following major groups:[29] 1. "True "True alkalo alkaloids" ids",, whic whichh cont contain ain nitrogen in the heterocycle and originate from [30] amino acids. acids. Their characteristic examples are atropine atropine,, nicotine and morphine morphine.. This group also includes some alkaloids which beside nitrogen heterocycle contain terpene (e.g. evonine[31]) or peptide fragments (e.g. ergotamine[32]). This group also includes piperidine alkaloids coniine and coniceine[33] although they do not originate from amino acids.[34] 2. "Protoa "Protoalka lkaloi loids", ds", which which contai containn nitrogen and also originate from amino acids.[30] Examples include mescaline mescaline,, adrenaline and ephedrine ephedrine.. 3. Polyam Polyamine ine alka alkaloi loids ds – deri derivat vative ivess of putrescine, putrescine, spermidine and spermine spermine.. [35] 4. Peptid Peptidee and cyclop cyclopept eptide ide alka alkaloi loids. ds. 5. Pseudalkaloi Pseudalkaloids ds – alkaloid-li alkaloid-like ke compounds compounds which which do not originate originate from amino [36] acids. This group includes, terpene terpene-like -like and steroid steroid-like -like alkaloids,[37] as well as purine-like purine -like alkaloids such as caffeine caffeine,, theobromine and theophylline theophylline..[38] Some authors classify as pseudoalkaloids such compounds such as ephedrine and cathinone.. Those originate from the amino acid phenylalanine cathinone acid phenylalanine,, but acquire their [38][39] [39] nitrogen atom not from the amino acid but through transamination transamination..[38] Some alkaloids do not have the carbon skeleton characteristic of their group. So, galantamine and homoaporphines do not contain isoquinoline fragment, but are generally attributed to isoquinoline alkaloids.[40] Main classes of monomeric alkaloids are listed in the table below: Class
Major groups Main synthesis steps Alkaloids with nitrogen heterocycles (true alkaloids)
Pyrrolidine derivatives[41]
Tropane derivatives[44]
Pyrrolizidine derivatives[47]
Examples
Ornithine or arginine or arginine → putrescine → N- Cuscohygrine Cuscohygrine,, methylputrescine → hygrine hygrine,, hygroline, 1 [41][43] 43] N-methyl-Δ stachydrine[41][ pyrroline [42] Atropine,, Atropine Ornithine or arginine or arginine scopolamine, scopolamine, Substitution in positions 3, 6 or 41][[44] 44][45] [45] → putrescine → N- hyoscyamine[41] 7 methylputrescine → N-methyl-Δ1Cocaine,, ecgonine [44] Cocaine Cocaine group [46] Substitution in positions 2 and 3 pyrroline [42]
Atropine group
Non-esters Complex esters of monocarboxylic acids Macrocyclic diesters
In plants: ornithine or Retronecine Retronecine,, arginine → heliotridine, [47][48] 48] putrescine → laburnine [47][ homospermidine → Indicine, lindelophin, retronecine [42] sarracine [47] Platyphylline,, Platyphylline
trichodesmine[47] 1-aminopyrrolizidines (lolines lolines)) Piperidine derivatives[52]
In fungi fungi:: L-proline + L-homoserine → N - Loline, N (3-amino-3formylloline, N carboxypropyl)prolin acetylloline[51] [49][50] [50] e → norloline[49] Sedamine,, lobeline, Sedamine Lysine → cadaverine anaferine, piperine anaferine, piperine → Δ1-piperideine [53] [33] [33][54] [54] Octanoic acid → Coniine,, coniceine Coniine coniceine → coniine [34] [34]
Lupinine group Quinolizidine [55][56] [56] derivatives[55]
Cytisine group Sparteine group Matrine group Ormosanine group
Indolizidine derivatives[61]
Simple derivatives of pyridine
Lupinine,, nupharidin Lupinine [55]
Cytisine [55] Sparteine,, lupanine Sparteine lupanine,, Lysine → cadaverine [55] 1 [57] anahygrine → Δ -piperideine Matrine, oxymatrine, [55][58][ [58][59] 59] allomatridine[55] Ormosanine, [55][60] [60] piptantine[55] Lysine → δsemialdehyde of αof αSwainsonine,, Swainsonine aminoadipic acid → castanospermine [63] pipecolic acid → 1 indolizidinone [62] Trigonelline,, Trigonelline ricinine, arecoline [64] [67]
Nicotinic acid → Nicotine,, Nicotine Pyridine Polycyclic noncondensing dihydronicotinic acid nornicotine, [64][65] [64] [65] derivatives pyridine derivatives → 1,2anabasine,, anatabine anabasine [66] [64][67] [64] [67] dihydropyridine Actinidine,, Actinidine Polycyclic condensed gentianine, pyridine derivatives pediculinine [68] Evonine, Sesquiterpene pyridine Nicotinic acid, acid, hippocrateine, derivatives isoleucine [11] [65][66] 66] triptonine [65][ Isoquinoline Simple derivatives of Tyrosine or Salsoline, [70] [69][70] 70] derivatives and isoquinoline phenylalanine → lophocerine [69][ related alkaloids Derivatives of 1- and 3- dopamine or N-methylcoridaldine, [69] [73] tyramine (for isoquinolines noroxyhydrastinine alkaloids Amarillis) [73]
[71][72] 72] Derivatives of 1- and 4- [71][ phenyltetrahydroisoquinoli nes [70] Derivatives of 5-naftilisoquinoline [75]
Derivatives of 1- and 2 benzyl-izoquinolines [76] Cularine group[77]
[70][74] 74] Cryptostilin [70][
Ancistrocladine [75] Papaverine, Papaverine, laudanosine,, laudanosine sendaverine Cularine, yagonine [77]
Pavines and isopavines [78] Benzopyrrocolines [79] Protoberberines [70] Phtalidisoquinolines [70] Spirobenzylisoquinolines [70]
[82]
Ipecacuanha alkaloids
Benzophenanthridines [70] Aporphines [70] Proaporphines [70] Homoaporphines [85] Homoproaporphines [85] Morphines[86]
Argemonine, amurensin [78] Cryptaustoline [70] Berberine,, canadine Berberine canadine,, ophiocarpine, mecambridine, corydaline [80] Hydrastine,, narcotine Hydrastine (Noscapine) [81] Fumaricine [78] Emetine, protoemetine, ipecoside [82] Sanguinarine, oxynitidine, corynoloxine [83] Glaucine,, coridine, Glaucine liriodenine [84] Pronuciferine, [70][79] [79] glaziovine [70] Kreysiginine, multifloramine [85] Bulbocodine [77] Morphine,, codeine Morphine codeine,, thebaine,, sinomenine thebaine [87]
Homomorphines [88] Tropoloisoquinolines [70] Azofluoranthenes [70] Amaryllis alkaloids[90]
Kreysiginine, androcymbine [86] Imerubrine [70] Rufescine, imeluteine [89] Lycorine,, ambelline, Lycorine tazettine,
Phenanthrene derivatives
galantamine, galantamine, montanine [91] Erysodine, erythroidine [74] Atherosperminine [70]
[70]
[80]
Erythrite alkaloids[74]
Protopins
Protopine, oxomuramine, corycavidine [83] Doriflavin [70]
[70]
Aristolactam [70] Oxazole derivatives[92] [93]
Annuloline, halfordinol, texaline, texamine[94]
Ibotenic acid → Muscimol
Ibotenic acid, Muscimol
Tyrosine → tyramine
Isoxazole derivatives
Thiazole derivatives[95]
Quinazoline derivatives[98]
Acridine derivatives[92]
1-Deoxy-D-xylulose 5-phosphate Nostocyclamide, [95][97] 97] (DOXP), tyrosine tyrosine,, thiostreptone [95][ cysteine [96] 3,4-Dihydro-4-quinazolone derivatives Anthranilic acid or 1,4-Dihydro-4-quinazolone phenylalanine or derivatives ornithine [99] Pyrrolidine and piperidine quinazoline derivatives Anthranilic acid [101]
Quinoline Simple derivatives of Anthranilic acid → [104][105] [104][ 105] derivatives quinoline derivatives of 2 - 3-carboxyquinoline [106] quinolones and 4quinolone Tricyclic terpenoids
Febrifugine[100] Glycorine, arborine, glycosminine[100] Vazicine (peganine) [92]
Rutacridone, 102][[103] acronicine[102] Cusparine, echinopsine,, echinopsine [105][107] [107][108] [108] evocarpine[105] [105][109] 109] Flindersine[105][
Dictamnine, Dictamnine, fagarine, [105][110] 110] skimmianine[105][
Furanoquinoline derivatives
[111]
Tryptophan → tryptamine → strictosidine (with secologanin)) → secologanin korinanteal → [72][106] 106] cinhoninon [72][
Quinines
Indole derivatives[87]
Quinine quinidine cinchonine,, cinchonine cinhonidine [109]
Non-isoprene indole alkaloids
Serotonin, Serotonin, psilocybin,, psilocybin dimethyltryptamine (DMT), bufotenin (DMT), bufotenin
Simple indole derivatives [112]
[114][115] [114][ 115]
See also: indole alkaloids
Tryptophan → Harman, harmine harmine,, tryptamine or 5harmaline,, eleagnine harmaline [113] [112] hydroxitriptofan Physostigmine (eserine), [117] Pyrroloindole alkaloids etheramine, physovenine, eptastigmine[117] Simple derivatives of βof β[116] carboline
Semiterpenoid indole alkaloids
Ergot alkaloids
Tryptophan → chanoclavine → agroclavine → elimoclavine → paspalic acid → lysergic acid [117]
[87]
Ergotamine, Ergotamine, ergobasine, ergosine[118]
Monoterpenoid indole alkaloids
Corynanthe type
alkaloids[113]
Iboga-type Iboga -type alkaloids[113] Aspidosperma-type Aspidosperma-type alkaloids[113]
Tryptophan → tryptamine → strictosidine (with secologanin)) [113] secologanin
Ajmalicine, sarpagine, vobasine, ajmaline,, yohimbine ajmaline yohimbine,, reserpine,, reserpine [119][120] 120] mitragynine,,[119][ mitragynine group strychnine and (Strychnine Strychnine brucine brucine,, aquamicine, vomicine [121]) Ibogamine,, ibogaine Ibogamine ibogaine,, [113] voacangine Vincamine,, Vincamine vincotine,
aspidospermine[122] [123]
Imidazole derivatives[92]
Purine derivatives[125]
Directly from histidine[124]
Histamine, Histamine, pilocarpine, pilosine, [92][124] [124] stevensine[92]
Xanthosine (formed in purine biosynthesis) → 7 methylxantosine → 7-methyl xanthine → theobromine → caffeine [72]
Caffeine theobromine theophylline [126][127] 127] saxitoxin [126][
Alkaloids with nitrogen in the side chain (protoalkaloids)
βPhenylethylamine derivatives[79]
Tyrosine or phenylalanine → dioxyphenilalanine → dopamine → Tyramine,, ephedrine Tyramine ephedrine,, adrenaline and pseudoephedrine,, pseudoephedrine mescaline tyrosine → mescaline mescaline,, cathinone cathinone,, tyramine catecholamines phenylalanine → 1- (adrenaline adrenaline,, phenylpropane-1,2- noradrenaline noradrenaline,, [11][129] 129] dione → cathinone dopamine dopamine))[11][ → ephedrine and pseudoephedrine [11] [39][128] [39][ 128]
Colchicine alkaloids [130]
Muscarine [132]
Benzylamine[134]
Tyrosine or phenylalanine → dopamine → autumnaline → colchicine [131]
Colchicine, Colchicine, colchamine[130]
Glutamic acid → 3ketoglutamic acid → muscarine (with pyruvic acid) acid)[133]
Muscarine, Muscarine, allomuscarine, epimuscarine, epiallomuscarine[132]
Phenylalanine with valine,, leucine or valine isoleucine[135] Polyamines alkaloids
Capsaicin, Capsaicin, dihydrocapsaicin,, dihydrocapsaicin nordihydrocapsaicin [134][136] [134][ 136]
Putrescine derivatives[137]
Paucine [137] ornithine → putrescine → spermidine → spermine[138]
Spermidine derivatives[137] Spermine derivatives[137]
Lunarine, codonocarpine[137] Verbascenine, aphelandrine [137]
Peptide (cyclopeptide) alkaloids
Peptide alkaloids Numularine C type with a 13membered cycle Ziziphin type [35][139] [35] [139] Frangulanine type Peptide alkaloids Scutianine A type with a 14membered cycle Integerrine type [35][139] [35] [139]
Amphibine F type Amfibine B type
Numularine C, numularine S [35] Ziziphin A, sativanine H [35] Frangulanine, From different amino scutianine J [139] acids [35] Scutianine A [35] Integerrine, discarine D [139] Amphibine F, spinanine A [35] Amphibine B, lotusine C [35]
Peptide alkaloids with a 15Mucronine A type membered cycle
[32][139] 139] Mucronine A [32][
[139]
Pseudoalkaloids ( terpenes terpenes and steroids steroids )
Diterpenes [32] Licoctonine type
Mevalonic acid → izopentenilpyrophosf Aconitine Aconitine,, delphinine [32][142] [32] [142] ate → geranyl [140][141] 141] pyrophosphate [140][
Steroids[143] Cholesterol, Cholesterol, arginine[144]
[edit edit]] Properties
Solasodine, solanidine,, solanidine veralkamine[145]
Head of a lamb born by a sheep which ate leaves of the corn lily plant. The cyclopia in the calf is induced by the alkaloid cyclopamine cyclopamine present present in the plant. Most alkaloids contain oxygen; those compounds are usually colorless crystals at ambient conditions. Oxygen-free alkaloids, such as nicotine[146] or coniine or coniine,,[22] are typically volatile, colorless, oily liquids.[147] Some alkaloids are colored, like berberine like berberine (yellow) and [147] sanguinarine (orange). Most alkaloid are weak bases, but some are amphoteric amphoteric,, for example theobromine and [148] theophylline). theophylline ). Most alkaloids are poorly soluble in water but readily dissolve in organic solvents, solvents, such as diethyl ether , chloroform and 1,2-dichloroethane 1,2-dichloroethane.. However, [148] caffeine dissolves well in boiling water. With acids acids,, alkaloids form salts of various strengths. Those salts are usually soluble in water and alcohol and poorly soluble in most organic solvents. Exceptions include scopolamine hydrobromide which is soluble in organic solvents and water-soluble quinine sulfate.[147] Most alkaloids have a bitter flavor bitter flavor . It is believed that plants evolved the ability to produce these bitter substances, many of which are poisonous, in order to protect themselves from animals; however, animals in turn evolved the ability to detoxify alkaloids.[149] Some alkaloids can produce developmental defects in the offspring of animals that consume them but cannot detoxify them. A characteristic example is the alkaloid cyclopamine cyclopamine,, which is present in the leaves of corn of corn lily. lily. During the 1950s, up to 25% lambs born by sheep that had grazed on corn lily suffered serious facial defects. Those defects ranged from deformed jaws to cyclopia (see picture). After decades of research, in 1980s, the substance that was responsible for the deformities was identified as the alkaloid 11deoxyjervine, which was renamed cyclopamine.[150]
[edit edit]] Distribution in nature
Strychnine tree. tree. Its seeds are rich in strychnine and brucine and brucine.. Alkaloids are generated by various living organisms, especially by higher plants – about [151][152] 152] 10 to 25% of those contain alkaloids.[151][ Therefore, in the past the term "alkaloid" was [153] associated with plants. The alkaloids content in plants is usually within a few percent and is inhomogeneous over the plant tissues. Depending on the type of plants, the maximum concentration is observed in the leaves ( black black henbane), henbane), fruits or seeds or seeds (Strychnine tree), tree), root (Rauwolfia (Rauwolfia [154] serpentina)) or bark (cinchona serpentina (cinchona). ). Furthermore, different tissues of the same plants may [155] contain different alkaloids. Beside plants, alkaloids are found in certain types of fungi of fungi,, such as psilocybin as psilocybin in the fungus of the genus Psilocybe Psilocybe,, and in animals, such as bufotenin as bufotenin in the skin of some [14] toads. Many marine organisms also contain alkaloids. alkaloids.[156] Some amines amines,, such as adrenaline and serotonin serotonin,, which play an important role in higher animals, are similar to alkaloids in their structure and biosynthesis and are sometimes called alkaloids. alkaloids.[157]
[edit edit]] Extraction
Crystals of piperine piperine extracted from black from black pepper .
Because of the structural diversity of alkaloids, there is no single method of their extraction from natural raw materials. materials.[158] Most methods exploit the property of most alkaloids to be soluble in organic solvents but not in water, and the opposite tendency of their salts. Most plants contain several alkaloids. Their mixture is extracted first and then individual [158][160] 160] alkaloids are separated.[159] Plants are thoroughly ground before extraction. extraction.[158][ Most [158] alkaloids are present in the raw plants in the form of salts of organic acids. acids. The [159] extracted alkaloids may remain salts or change into bases. Base extraction is achieved by processing the raw material with alkaline solutions and extracting the alkaloid bases with organic solvents, such as 1,2-dichloroethane, chloroform, diethyl ether or benzene. Then, the impurities are dissolved by weak acids; this converts alkaloid bases into salts which are washed away with water. If necessary, an aqueous solution of alkaloid salts is again made alkaline and treated with an organic solvent. The process is repeated until the desired purity is achieved. In the acidic extraction, the raw plant material is processed by a weak acidic solution (e.g., acetic acid in water, ethanol or methanol). A base is then added to convert alkaloids to basic forms which are extracted with organic solvent (if the extraction was performed with alcohol, it is removed first, and the remainder is dissolved in water). The solution is [158][161] 161] purified as described above. above.[158][ Alkaloids are separated from their mixture using their different solubility in certain solvents and different reactivity with certain reagents or by distillation distillation..[162]
[edit edit]] Biosynthesis Biological precursors of most alkaloids are amino acids, acids, such as ornithine ornithine,, lysine lysine,, phenylalanine,, tyrosine phenylalanine tyrosine,, tryptophan tryptophan,, histidine histidine,, aspartic acid and anthranilic acid. acid.[163] Nicotinic acid can be synthesized from tryptophan or aspartic acid. Ways of alkaloid biosynthesis are too numerous and can not be easily classified. classified.[72] However, there are a few typical reactions involved in the biosynthesis of various classes of alkaloids, including synthesis of Schiff of Schiff bases and Mannich reaction. reaction.[163] [edit edit]] Synthesis of Schiff bases
Main article: Schiff base Schiff bases can be obtained by reacting amines with ketones or aldehydes.[164] These reactions are a common method of producing C=N bonds.[165]
In the biosynthesis of alkaloids, such reactions may take place within a molecule, molecule,[163] such as in the synthesis of piperidine:[28]
[edit edit]] Mannich reaction
Main article: Mannich reaction An integral component of the Mannich reaction, in addition to an amine and a carbonyl compound, is a carbanion carbanion,, which plays the role of the nucleophile in the nucleophilic addition to the ion formed by the reaction of the amine and the carbonyl. carbonyl.[165]
[166][167] 167] The Mannich reaction can proceed both intermolecularly and intramolecularly:[166][
[edit edit]] Dimer alkaloids In addition to the described above monomeric alkaloids, there are also dimeric dimeric,, and even trimeric and tetrameric alkaloids formed upon condensation of two, three and four monomeric alkaloids. Dimeric alkaloids are usually formed from monomers of the same type through the following mechanisms:[168] • • •
Mannich reaction, reaction, resulting in, e.g., voacamine Michael reaction (villalstonine). Condensation of aldehydes with amines (toxiferine).
• •
Oxidative addition of phenols (dauricine, tubocurarine). Lactonization (carpaine). •
Voacamine.svg Voacamine
•
Villalstonine
•
Toxiferine
•
Dauricine
•
Tubocurarine
•
Carpaine
[edit edit]] The biological role The role of alkaloids for living organisms which produce them is still unclear.[169] Initially it was assumed that the alkaloids are the final products of nitrogen of nitrogen metabolism in plants, and urea in mammals. Later it was shown that alkaloid concentrations varies over time and this hypothesis was refuted.[7] Most of the known functions of alkaloids are related to protection. For example, aporphine alkaloid liriodenine produced by the tulip tree protects it from parasitic mushrooms. In addition, presence of alkaloids in the plant prevents insects and chordate animals from eating it. However, some animals adapted to alkaloids and even use them in their own metabolism.[170] Such alkaloid-related substances as serotonin serotonin,, dopamine and histamine are important neurotransmitters in animals. Alkaloids are also known to regulate plant growth.[171]
[edit edit]] Applications [edit edit]] In medicine
Medical use of alkaloid plants has a long history, and thus when the first alkaloids were synthesized in the 19th century, they immediately found application in clinical practice. [172] Many alkaloids are still used in medicine, usually in the form of salts, including the [7][173] [173] following:[7] : Alkaloid
Action
Ajmaline antiarrhythmic Atropine,, scopolamine Atropine scopolamine,, hyoscyamine anticholinergic Vinblastine,, vincristine Vinblastine antitumor Vincamine vasodilating,, antihypertensive vasodilating Codeine cough medicine Cocaine anesthetic Colchicine remedy for gout for gout Morphine analgesic Reserpine antihypertensive
Tubocurarine Physostigmine Quinidine Quinine Emetine Ergot alkaloids
Muscle relaxant inhibitor of acetylcholinesterase of acetylcholinesterase antiarrhythmic antipyretics, antimalarial antiprotozoal agent sympathomimetic,, vasodilator, antihypertensive sympathomimetic
Many synthetic and semisynthetic drugs are structural modifications of the alkaloids, which were designed to enhance or change the primary effect of the drug and reduce unwanted side effects.[174] For example, naloxone naloxone,, an opioid receptor antagonist receptor antagonist,, is a [175] derivative of thebaine of thebaine which is present in opium opium..
•
Thebaine
•
Naloxone [edit edit]] In agriculture
Prior to the development of a wide range of relatively low-toxic synthetic pesticides synthetic pesticides,, some alkaloids, such as salts of nicotine and anabasine anabasine,, were used as insecticides insecticides.. Their [176] use was limited by their high toxicity to humans. [edit edit]] Use as psychoactive drugs
Preparations of plants containing alkaloids and their extracts, and later pure alkaloids have long been used as psychoactive as psychoactive substances. substances. Cocaine and cathinone are stimulants of [177][178] [177][ 178] the central nervous system. system. Mescaline and many of indole alkaloids (such as [179][180] [180] psilocybin,, dimethyltryptamine and ibogaine psilocybin ibogaine)) have hallucinogenic effect.[179] Morphine and codeine are strong narcotic pain killers.[181]
There are alkaloids that do not have strong psychoactive effect themselves, but are precursors for semi-synthetic psychoactive drugs. For example, ephedrine and pseudoephedrine are used to produce methcathinone (ephedrine) and methamphetamine methamphetamine.. [182]
[edit edit]] See also • • • •
Amine Base (chemistry) Natural products Secondary metabolite
[edit edit]] Notes ^ In the penultimate sentence of his article [W. Meissner (1819) "Über 1. Pflanzenalkalien: II. Über ein neues Pflanzenalkali (Alkaloid)" (On plant alkalis: II. On a new plant alkali (alkaloid)), Journal für Chemie und Physik , vol. 25, pp. 377–381] Meissner wrote "Überhaupt scheint es mir auch angemessen, die bis jetzt bekannten Pflanzenstoffe nicht mit dem Namen Alkalien, sondern Alkaloide zu belegen, da sie doch in manchen Eigenschaften von den Alkalien sehr abweichen, sie würden daher in dem Abschnitt der Pflanzenchemie vor den Pflanzensäuren ihre Stelle finden." (In general, it seems appropriate to me to impose on the known plant substances not the name "alkalis" but "alkaloids", since they differ greatly in some properties from the alkalis; among the chapters of plant chemistry, they would therefore find their place before plant acids [since "Alkaloid" would precede "Säure" (acid)].)
[edit edit]] References ^ Andreas Luch (2009). Molecular, clinical and environmental toxicology. 1. Springer. p. 20. ISBN 3764383356 3764383356.. a b 2. ^ IUPAC. Compendium of Chemical Terminology, Terminology, 2nd ed. (The "Gold Book"). Compiled by A. D. McNaught and A. Wilkinson. Blackwell Scientific Publications, Oxford (1997) ISBN 0-9678550-9-8 doi doi::10.1351/goldbook ^ R. H. F. Manske. The Alkaloids. Chemistry and Physiology. Volume 3. VIII. - New York: Academic Press, Press, 1965, p. 673 ^ Robert Alan Lewis. Lewis' dictionary of toxicology. CRC Press, 1998, p. 4. 51 ISBN 1-56670-223-2 5. ^ a b c d Chemical Encyclopedia: alkaloids ^ Rhoades, David F (1979). "Evolution of Plant Chemical Defense against 6. Herbivores". In Rosenthal, Gerald A., and Janzen, Daniel H. Herbivores: Their Interaction with Secondary Plant Metabolites. New York: Academic Press. p. 41. ISBN 0-12-597180-X 0-12-597180-X..
7.
^ a b c Robert A. Meyers Encyclopedia of Physical Science and Technology, Eighteen-Volume Set, Third Edition. - Alkaloids ISBN 0-12-2274113 ^ Leland J. Cseke Natural 8. Cseke Natural Products from Plants Second Edition. - CRC, 2006, p. 30 ISBN 0-8493-2976-0 ^ A. William Johnson Invitation to Organic Chemistry, 9. Chemistry, Jones and Bartlett, 1999, p. 433 ISBN 0-7637-0432-6 ^ Raj K Bansal A Text Book of Organic Chemistry. 10. Chemistry. 4th Edition, New Age International, 2004, p. 644 ISBN 81-224-1459-1 11. ^ a b c d Aniszewski, p. 110 ^ Biographical information about German pharmacist Carl Friedrich 12. Wilhelm Meißner (1792-1853) is available in the German Wikipedia: http://de.wikipedia.org/wiki/Carl_Friedrich_Wilhelm_Mei%C3%9Fner (in http://de.wikipedia.org/wiki/Carl_Friedrich_Wilhelm_Mei%C3%9Fner (in German). ^ Hesse, pp. 1–3 13. 14. ^ a b Hesse, p. 5 ^ The suffix "-ine" is a Greek feminine patronymic suffix and thus means 15. "daughter of"; hence, for example, "atropine" means "daughter of Atropa (belladonna)". See: https://webspace.yale.edu/chem125/125/history99/5Valence/Nomenclature/alkane names.html . ^ Hesse, p. 7 16. 17. ^ a b Aniszewski, p. 182 ^ Hesse, p. 338 18. ^ Hesse, p. 304 19. ^ Hesse, p. 350 20. ^ Hesse, pp. 313–316 21. 22. ^ a b TSB: Coniine ^ Hesse, p. 204 23. ^ Begley Encyclopedia of Chemical Biology: Natural Products in Plants, 24. Chemical Diversity of
25. ^ a b Hesse, p. 11 ^ Orekhov, p. 6 26. ^ Aniszewski, p. 109 27. 28. ^ a b Dewick, p. 307 ^ Hesse, p. 12 29. 30. ^ a b Plemenkov, p. 223 ^ Aniszewski, p. 108 31. 32. ^ a b c d Hesse, p. 84 33. ^ a b Hesse, p. 31 34. ^ a b c Dewick, p. 381 35. ^ a b c d e f g g h i Dimitris C. Gournelif, Gregory G. Laskarisb and Robert Verpoorte (1997). "Cyclopeptide alkaloids". Nat. Prod. Rep. 14 (1): 75–82. doi::10.1039/NP9971400075 doi 10.1039/NP9971400075.. PMID 9121730 9121730.. ^ Aniszewski, p. 11 36. ^ Plemenkov, p. 246 37.
38. ^ a b Aniszewski, p. 12 39. ^ a b Dewick, p. 382 ^ Hesse, pp. 44, 53 40. 41. ^ a b c Plemenkov, p. 224 42. ^ a b c Aniszewski, p. 75 ^ Orekhov, p. 33 43. 44. ^ a b c Chemical Encyclopedia: Tropan alkaloids ^ Hesse, p. 34 45. ^ Aniszewski, p. 27 46. 47. ^ a b c d Chemical Encyclopedia: Pyrrolizidine alkaloids ^ Plemenkov, p. 229 48. ^ Blankenship JD, Houseknecht JB, Pal S, Bush LP, Grossman RB, 49. Schardl CL (2005). "Biosynthetic precursors of fungal pyrrolizidines, the loline alkaloids". Chembiochem 6 (6): 1016–1022. doi doi::10.1002/cbic.200400327 10.1002/cbic.200400327.. PMID 15861432 15861432.. ^ Faulkner JR, Hussaini SR, Blankenship JD, Pal S, Branan BM, 50. Grossman RB, Schardl CL (2006). "On the sequence of bond formation in loline alkaloid biosynthesis". Chembiochem 7 (7): 1078–1088. doi::10.1002/cbic.200600066 doi 10.1002/cbic.200600066.. PMID 16755627 16755627.. ^ Schardl CL, Grossman RB, Nagabhyru P, Faulkner JR, Mallik UP 51. (2007). "Loline alkaloids: currencies of mutualism". Phytochemistry 68 (7): 980– 996. doi doi::10.1016/j.phytochem.2007.01.010 10.1016/j.phytochem.2007.01.010.. PMID 17346759 17346759.. ^ Plemenkov, p. 225 52. ^ Aniszewski, p. 95 53. ^ Orekhov, p. 80 54. 55. ^ a b c d e f Chemical Encyclopedia: Quinolizidine alkaloids ^ J. E. Saxton The Alkaloids. A Specialist Periodical Report . Volume 1. 56. London: The Chemical Society, 1971, p. 93 ^ Aniszewski, p. 98 57. ^ J. E. Saxton The Alkaloids. A Specialist Periodical Report . Volume 1. 58. London: The Chemical Society, 1971, p. 91 ^ Joseph P. Michael (2002). "Indolizidine and quinolizidine alkaloids". 59. Nat. Prod. Rep 19: 458–475. doi doi::10.1039/b208137g 10.1039/b208137g.. ^ J. E. Saxton The Alkaloids. A Specialist Periodical Report . Volume 1. 60. London: The Chemical Society, 1971, p. 92 ^ Dewick, p. 310 61. ^ Aniszewski, p. 96 62. ^ Aniszewski, p. 97 63. 64. ^ a b c Plemenkov, p. 227 65. ^ a b Chemical Encyclopedia: pyridine alkaloids 66. ^ a b Aniszewski, p. 107 67. ^ a b Aniszewski, p. 85 ^ Plemenkov, p. 228 68. 69. ^ a b Hesse, p. 36 70. ^ a b c d e f g g h i i j j k l m n o p q r r s s t Chemical Encyclopedia: isoquinoline alkaloids ^ Aniszewski, pp. 77–78 71.
72. ^ a b c d Tadhg P. Begley.Encyclopedia of Chemical Biology: Alkaloid Biosynthesis 73. ^ a b J. E. Saxton The Alkaloids. A Specialist Periodical Report . Volume 3. - London: The Chemical Society, 1973, p. 122 74. ^ a b c Hesse, p. 54 75. ^ a b Hesse, p. 37 ^ Hesse, p. 38 76. 77. ^ a b c Hesse, p. 46 78. ^ a b c Hesse, p. 50 79. ^ a b c Kenneth W. Bentley (1997). "β-Phenylethylamines and the isoquinoline alkaloids". Nat. Prod. Rep 14 (4): 387–411. doi::10.1039/NP9971400387 doi 10.1039/NP9971400387.. PMID 9281839 9281839.. a b 80. ^ Hesse, p. 47 ^ Hesse, p. 39 81. 82. ^ a b Hesse, p. 41 83. ^ a b Hesse, p. 49 ^ Hesse, p. 44 84. 85. ^ a b c J. E. Saxton The Alkaloids. A Specialist Periodical Report . Volume 3. - London: The Chemical Society, 1973, p. 164 86. ^ a b Hesse, p. 51 87. ^ a b c Plemenkov, p. 236 ^ J. E. Saxton The Alkaloids. A Specialist Periodical Report . Volume 3. 88. London: The Chemical Society, 1973, p. 163 ^ J. E. Saxton The Alkaloids. A Specialist Periodical Report . Volume 3. 89. London: The Chemical Society, 1973, p. 168 ^ Hesse, p. 52 90. ^ Hesse, p. 53 91. 92. ^ a b c d e Plemenkov, p. 241 ^ Arnold Brossi The Alkaloids: Chemistry and Pharmacology, Volume 93. 35. - Academic Press, 1989, p. 261 ^ Arnold Brossi The Alkaloids: Chemistry and Pharmacology, Volume 94. 35. - Academic Press, 1989, pp. 260–263 95. ^ a b Plemenkov, p. 242 ^ Tadhg P. Begley.Encyclopedia of Chemical Biology: Cofactor 96. Biosynthesis ^ John R. Lewis (2000). "Amaryllidaceae, muscarine, imidazole, oxazole, 97. thiazole and peptide alkaloids, and other miscellaneous alkaloids". alkaloids". Nat. Prod. Rep 17 (1): 57–84. doi doi::10.1039/a809403i 10.1039/a809403i.. PMID 10714899 10714899.. ^ Chemical Encyclopedia: Quinazoline alkaloids 98. ^ Aniszewski, p. 106 99. 100. ^ a b Aniszewski, p. 105 101. ^ Richard B. Herbert; Herbert, Richard B.; Herbert, Richard B. (1999). "The biosynthesis of plant alkaloids and nitrogenous microbial metabolites". metabolites". Nat. Prod. Rep 16: 199–208. doi doi::10.1039/a705734b 10.1039/a705734b.. 102. ^ Plemenkov, pp. 231, 246 103. ^ Hesse, p. 58
104. ^ Plemenkov, p. 231 105. ^ a b c d Chemical Encyclopedia: Quinoline alkaloids 106. ^ a b Aniszewski, p. 114 107. ^ Orekhov, p. 205 108. ^ Hesse, p. 55 109. ^ a b Plemenkov, p. 232 110. ^ Orekhov, p. 212 111. ^ Aniszewski, p. 118 112. ^ a b Aniszewski, p. 112 113. ^ a b c d e f Aniszewski, p. 113 114. ^ Hesse, p. 15 115. ^ J. E. Saxton The Alkaloids. A Specialist Periodical Report . Volume 1. London: The Chemical Society, 1971, p. 467 116. ^ Dewick, p. 349-350 117. ^ a b c Aniszewski, p. 119 118. ^ Hesse, p. 29 119. ^ Hesse, pp. 23-26 120. ^ J. E. Saxton The Alkaloids. A Specialist Periodical Report . Volume 1. London: The Chemical Society, 1971, p. 169 121. ^ J. E. Saxton The Alkaloids. A Specialist Periodical Report . Volume 5. London: The Chemical Society, 1975, p. 210 122. ^ Hesse, pp. 17-18 123. ^ Dewick, p. 357 124. ^ a b Aniszewski, p. 104 125. ^ Hesse, p. 72 126. ^ Hesse, p. 73 127. ^ Dewick, p. 396 128. ^ PlantCyc Pathway: ephedrine biosynthesis 129. ^ Hesse, p. 76 130. ^ a b Chemical Encyclopedia: colchicine alkaloids 131. ^ Aniszewski, p. 77 132. ^ a b Hesse, p. 81 133. ^ Arnold Brossi The Alkaloids: Chemistry and Pharmacology, Volume 23. - Academic Press, 1984, p. 376 134. ^ a b Hesse, p. 77 135. ^ Arnold Brossi The Alkaloids: Chemistry and Pharmacology, Volume 23. - Academic Press, 1984, p. 268 136. ^ Arnold Brossi The Alkaloids: Chemistry and Pharmacology, Volume 23. - Academic Press, 1984, p. 231 137. ^ a b c d e f Hesse, p. 82 138. ^ Spermine Biosynthesis 139. ^ a b c d e f Plemenkov, p. 243 140. ^ Chemical Encyclopedia: Terpenes 141. ^ Tadhg P. Begley.Encyclopedia of Chemical Biology: Natural Products: An Overview
142. ^ Atta-ur-Rahman and M. Iqbal Choudhary (1997). "Diterpenoid and steroidal alkaloids". alkaloids". Nat. Prod. Rep 14 (2): 191–203. doi doi::10.1039/np9971400191 10.1039/np9971400191.. PMID 9149410 9149410.. 143. ^ Hesse, p. 88 144. ^ Dewick, p. 388 145. ^ Plemenkov, p. 247 146. ^ TSB: Nicotine 147. ^ a b c Grinkevich, p. 131 148. ^ a b G. A. Spiller Caffeine, CRC Press, 1997 ISBN 0-8493-2647-8 149. ^ Fattorusso, p. 53 150. ^ Thomas Acamovic, Colin S. Stewart, T. W. Pennycott (2004). Poisonous plants and related toxins, Volume 2001. CABI. p. 362. ISBN 0851996140 0851996140.. 151. ^ Aniszewski, p. 13 152. ^ Orekhov, p. 11 153. ^ Hesse, p.4 154. ^ Grinkevich, pp. 122-123 155. ^ Orekhov, p. 12 156. ^ Fattorusso, p. XVII 157. ^ Aniszewski, pp. 110–111 158. ^ a b c d Hesse, p. 116 159. ^ a b Grinkevich, p. 132 160. ^ Grinkevich, p. 5 161. ^ Grinkevich, pp. 132-134 162. ^ Grinkevich, pp. 134-136 163. ^ a b c Plemenkov, p. 253 164. ^ Plemenkov, p. 254 165. ^ a b Dewick, p. 19 166. ^ Plemenkov, p. 255 167. ^ Dewick, p. 305 168. ^ Hesse, pp. 91–105 169. ^ Aniszewski, p. 142 170. ^ Hesse, pp. 283-291 171. ^ Aniszewski, pp. 142-143 172. ^ Hesse, p. 303 173. ^ Hesse, pp. 303-309 174. ^ Hesse, p. 309 175. ^ Dewick, p. 335 176. ^ György Matolcsy, Miklós Nádasy, Viktor Andriska Pesticide chemistry, Elsevier, 2002, pp. 21-22 ISBN 0-444-98903-X 177. ^ Veselovskaya, p. 75 178. ^ Hesse, p. 79 179. ^ Veselovskaya, p. 136 180. ^ Geoffrey A. Cordell The Alkaloids: Chemistry and Biology. Volume 56, Elsevier, 2001, p. 8 181. ^ Veselovskaya, p. 6
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^ Veselovskaya, pp. 51-52
[edit edit]] Bibliography Wikimedia Commons has media related to: Alkaloid •
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Tadeusz Aniszewski (2007). Alkaloids - secrets of life. Amsterdam: Elsevier . ISBN 978-0-444-52736-3 978-0-444-52736-3.. Tadhg P. Begley (2009). Encyclopedia of Chemical Biology. Wiley. ISBN 978-0471-75477-0.. 471-75477-0 Knunyants IL (1988). Chemical Encyclopedia. Soviet Encyclopedia. Paul M Dewick (2002). Medicinal Natural Products. A Biosynthetic Approach. Second Edition. Wiley. ISBN 0471496405 0471496405.. E. Fattorusso and O. Taglialatela-Scafati (2008). Modern Alkaloids: Structure, Isolation, Synthesis and Biology. Wiley-VCH. ISBN 978-3-527-31521-5 978-3-527-31521-5.. Grinkevich NI Safronich LN (1983). The chemical analysis of medicinal plants: Proc. allowance for pharmaceutical universities. M. Manfred Hesse (2002). Alkaloids: Nature's Curse or Blessing?. Wiley-VCH. ISBN 978-3-906390-24-6 978-3-906390-24-6.. Orekhov AP (1955). Chemistry alkaloids (Acad. 2 ed.). M.: USSR. Plemenkov VV (2001). Introduction to the Chemistry of Natural Compounds. Kazan. N. B. Veselovskaya, AE Kovalenko Drugs, M.: Triada-X, 2000 [hide hide]]v · d · eAlkaloid groups
Indole:: Indole
5-MeO-DMT | Dimethyltryptamine | Harmala alkaloids | Psilocin | Psilocybin | Reserpine | Serotonin | Tryptamine | Yohimbine
Phenethylamine:: Phenethylamine
Amphetamine | Cathinone | Dopamine | Ephedrine | Mescaline | Methamphetamine | Phenethylamine | Tyramine
Purine:: Purine
Caffeine | Theobromine | Theophylline
Pyridine:: Pyridine
Coniine
Pyrrolidine:: Pyrrolidine
Nicotine
Quinoline:: Quinoline
Quinine
Isoquinoline:: Isoquinoline
Codeine | Morphine
Tropane:: Tropane
Atropine | Cocaine | Hyoscyamine | Scopolamine
Terpenoid:: Terpenoid
Aconitine | Solanine
Betaines:: Betaines
Choline | Muscarine
biochemical families families:: prot · nucl · carb (glpr , alco alco,, glys glys)) · lipd (fata fata//i, phld phld,, strd strd,, gllp gllp,, eico)) · amac eico amac//i · ncbs ncbs//i · ttpy ttpy//i
Categories:: Metabolism | Alkaloids Categories •
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