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Alkaloid

April 30, 2023

This article is about the class of chemical compounds. For the pharmaceutical company, see Alkaloid (company).

Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral[2] and even weakly acidic properties.[3] Some synthetic compounds of similar structure may also be termed alkaloids.[4] In addition to carbon, hydrogen and nitrogen, alkaloids may also contain oxygen, sulfur and, more rarely, other elements such as chlorine, bromine, and phosphorus.[5]

The first individual alkaloid, morphine, was isolated in 1804 from the opium poppy (Papaver somniferum).[1]

Alkaloids are produced by a large variety of organisms including bacteria, fungi, plants, and animals.[6] They can be purified from crude extracts of these organisms by acid-base extraction, or solvent extractions followed by silica-gel column chromatography.[7] Alkaloids have a wide range of pharmacological activities including antimalarial (e.g. quinine), antiasthma (e.g. ephedrine), anticancer (e.g. homoharringtonine),[8] cholinomimetic (e.g. galantamine),[9] vasodilatory (e.g. vincamine), antiarrhythmic (e.g. quinidine), analgesic (e.g. morphine),[10] antibacterial (e.g. chelerythrine),[11] and antihyperglycemic activities (e.g. piperine).[12][failed verification] Many have found use in traditional or modern medicine, or as starting points for drug discovery. Other alkaloids possess psychotropic (e.g. psilocin) and stimulant activities (e.g. cocaine, caffeine, nicotine, theobromine),[13] and have been used in entheogenic rituals or as recreational drugs. Alkaloids can be toxic too (e.g. atropine, tubocurarine).[14] Although alkaloids act on a diversity of metabolic systems in humans and other animals, they almost uniformly evoke a bitter taste.[15]

The boundary between alkaloids and other nitrogen-containing natural compounds is not clear-cut.[16] Compounds like amino acid peptides, proteins, nucleotides, nucleic acid, amines, and antibiotics are usually not called alkaloids.[2] Natural compounds containing nitrogen in the exocyclic position (mescaline, serotonin, dopamine, etc.) are usually classified as amines rather than as alkaloids.[17] Some authors, however, consider alkaloids a special case of amines.[18][19][20]

Naming

 
The article that introduced the concept of "alkaloid".

The name "alkaloids" (German: Alkaloide) was introduced in 1819 by the German chemist Carl Friedrich Wilhelm Meißner, and is derived from late Latin root alkali and the Greek-language suffix -οειδής -('like').[nb 1] However, the term came into wide use only after the publication of a review article, by Oscar Jacobsen in the chemical dictionary of Albert Ladenburg in the 1880s.[21][22]

There is no unique method for naming alkaloids.[23] Many individual names are formed by adding the suffix "ine" to the species or genus name.[24] For example, atropine is isolated from the plant Atropa belladonna; strychnine is obtained from the seed of the Strychnine tree (Strychnos nux-vomica L.).[5] Where several alkaloids are extracted from one plant their names are often distinguished by variations in the suffix: "idine", "anine", "aline", "inine" etc. There are also at least 86 alkaloids whose names contain the root "vin" because they are extracted from vinca plants such as Vinca rosea (Catharanthus roseus);[25] these are called vinca alkaloids.[26][27][28]

History

 
Friedrich Sertürner, the German chemist who first isolated morphine from opium.

Alkaloid-containing plants have been used by humans since ancient times for therapeutic and recreational purposes. For example, medicinal plants have been known in Mesopotamia from about 2000 BC.[29] The Odyssey of Homer 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.[30] A Chinese book on houseplants written in 1st–3rd centuries BC mentioned a medical use of ephedra and opium poppies.[31] Also, coca leaves have been used by Indigenous South Americans since ancient times.[32]

Extracts from plants containing toxic alkaloids, such as aconitine and tubocurarine, were used since antiquity for poisoning arrows.[29]

Studies of alkaloids began in the 19th century. In 1804, the German chemist Friedrich Sertürner isolated from opium a "soporific principle" (Latin: principium somniferum), which he called "morphium", referring to Morpheus, the Greek 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.

A significant contribution to the chemistry of alkaloids in the early years of its development was made by the French researchers Pierre Joseph 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).[33] The development of the chemistry of alkaloids was accelerated by the emergence of spectroscopic and chromatographic methods in the 20th century, so that by 2008 more than 12,000 alkaloids had been identified.[34]

The first complete synthesis of an alkaloid was achieved in 1886 by the German chemist Albert Ladenburg. He produced coniine by reacting 2-methylpyridine with acetaldehyde and reducing the resulting 2-propenyl pyridine with sodium.[35][36]

 
Bufotenin, an alkaloid from some toads, contains an indole core, and is produced in living organisms from the amino acid tryptophan.

Classifications

 
The nicotine molecule contains both pyridine (left) and pyrrolidine rings (right).

Compared with most other classes of natural compounds, alkaloids are characterized by a great structural diversity. There is no uniform classification.[37] Initially, when knowledge of chemical structures was lacking, botanical classification of the source plants was relied on. This classification is now considered obsolete.[5][38]

More recent classifications are based on similarity of the carbon skeleton (e.g., indole-, isoquinoline-, and pyridine-like) or biochemical precursor (ornithine, lysine, tyrosine, tryptophan, etc.).[5] However, they require compromises in borderline cases;[37] for example, nicotine contains a pyridine fragment from nicotinamide and a pyrrolidine part from ornithine[39] and therefore can be assigned to both classes.[40]

Alkaloids are often divided into the following major groups:[41]

  1. "True alkaloids" contain nitrogen in the heterocycle and originate from amino acids.[42] Their characteristic examples are atropine, nicotine, and morphine. This group also includes some alkaloids that besides the nitrogen heterocycle contain terpene (e.g., evonine[43]) or peptide fragments (e.g. ergotamine[44]). The piperidine alkaloids coniine and coniceine may be regarded as true alkaloids (rather than pseudoalkaloids: see below)[45] although they do not originate from amino acids.[46]
  2. "Protoalkaloids", which contain nitrogen (but not the nitrogen heterocycle) and also originate from amino acids.[42] Examples include mescaline, adrenaline and ephedrine.
  3. Polyamine alkaloids – derivatives of putrescine, spermidine, and spermine.
  4. Peptide and cyclopeptide alkaloids.[47]
  5. Pseudoalkaloids – alkaloid-like compounds that do not originate from amino acids.[48] This group includes terpene-like and steroid-like alkaloids,[49] as well as purine-like alkaloids such as caffeine, theobromine, theacrine and theophylline.[50] Some authors classify ephedrine and cathinone as pseudoalkaloids. Those originate from the amino acid phenylalanine, but acquire their nitrogen atom not from the amino acid but through transamination.[50][51]

Some alkaloids do not have the carbon skeleton characteristic of their group. So, galanthamine and homoaporphines do not contain isoquinoline fragment, but are, in general, attributed to isoquinoline alkaloids.[52]

Main classes of monomeric alkaloids are listed in the table below:

Class Major groups Main synthesis steps Examples
Alkaloids with nitrogen heterocycles (true alkaloids)
Pyrrolidine derivatives[53]
 
 Ornithine or arginine → putrescine → N-methylputrescine → N-methyl-Δ1-pyrroline [54] Cuscohygrine, hygrine, hygroline, stachydrine[53][55]
Tropane derivatives[56]
 
 Atropine group
Substitution in positions 3, 6 or 7 		Ornithine or arginine → putrescine → N-methylputrescine → N-methyl-Δ1-pyrroline [54] Atropine, scopolamine, hyoscyamine[53][56][57]
Cocaine group
Substitution in positions 2 and 3 		Cocaine, ecgonine[56][58]
Pyrrolizidine derivatives[59]
 
 Non-esters In plants: ornithine or arginine → putrescine → homospermidine → retronecine[54] Retronecine, heliotridine, laburnine [59][60]
Complex esters of monocarboxylic acids Indicine, lindelophin, sarracine [59]
Macrocyclic diesters Platyphylline, trichodesmine[59]
1-aminopyrrolizidines (lolines) In fungi: L-proline + L-homoserine → N-(3-amino-3-carboxypropyl)proline → norloline[61][62] Loline, N-formylloline, N-acetylloline[63]
Piperidine derivatives[64]
 
 Lysine → cadaverine → Δ1-piperideine [65] Sedamine, lobeline, anaferine, piperine[45][66]
Octanoic acid → coniceine → coniine[46] Coniine, coniceine [46]
Quinolizidine derivatives[67][68]
 
 Lupinine group Lysine → cadaverine → Δ1-piperideine [69] Lupinine, nupharidin [67]
Cytisine group Cytisine[67]
Sparteine group Sparteine, lupanine, anahygrine[67]
Matrine group. Matrine, oxymatrine, allomatridine[67][70][71]
Ormosanine group Ormosanine, piptantine[67][72]
Indolizidine derivatives[73]
 
 Lysine → δ-semialdehyde of α-aminoadipic acid → pipecolic acid → 1 indolizidinone [74] Swainsonine, castanospermine[75]
Pyridine derivatives[76][77]
 
 Simple derivatives of pyridine Nicotinic acid → dihydronicotinic acid → 1,2-dihydropyridine [78] Trigonelline, ricinine, arecoline[76][79]
Polycyclic noncondensing pyridine derivatives Nicotine, nornicotine, anabasine, anatabine [76][79]
Polycyclic condensed pyridine derivatives Actinidine, gentianine, pediculinine [80]
Sesquiterpene pyridine derivatives Nicotinic acid, isoleucine[20] Evonine, hippocrateine, triptonine [77][78]
Isoquinoline derivatives and related alkaloids [81]
 
 Simple derivatives of isoquinoline [82] Tyrosine or phenylalanine → dopamine or tyramine (for alkaloids Amarillis) [83][84] Salsoline, lophocerine [81][82]
Derivatives of 1- and 3-isoquinolines [85] N-methylcoridaldine, noroxyhydrastinine [85]
Derivatives of 1- and 4-phenyltetrahydroisoquinolines [82] Cryptostilin [82][86]
Derivatives of 5-naftil-isoquinoline [87] Ancistrocladine [87]
Derivatives of 1- and 2-benzyl-izoquinolines [88] Papaverine, laudanosine, sendaverine
Cularine group[89] Cularine, yagonine [89]
Pavines and isopavines [90] Argemonine, amurensine[90]
Benzopyrrocolines [91] Cryptaustoline [82]
Protoberberines [82] Berberine, canadine, ophiocarpine, mecambridine, corydaline [92]
Phthalidisoquinolines [82] Hydrastine, narcotine (Noscapine) [93]
Spirobenzylisoquinolines [82] Fumaricine [90]
Ipecacuanha alkaloids[94] Emetine, protoemetine, ipecoside [94]
Benzophenanthridines [82] Sanguinarine, oxynitidine, corynoloxine [95]
Aporphines [82] Glaucine, coridine, liriodenine [96]
Proaporphines [82] Pronuciferine, glaziovine [82][91]
Homoaporphines [97] Kreysiginine, multifloramine [97]
Homoproaporphines [97] Bulbocodine [89]
Morphines[98] Morphine, codeine, thebaine, sinomenine[99]
Homomorphines [100] Kreysiginine, androcymbine [98]
Tropoloisoquinolines [82] Imerubrine [82]
Azofluoranthenes [82] Rufescine, imeluteine [101]
Amaryllis alkaloids[102] Lycorine, ambelline, tazettine, galantamine, montanine [103]
Erythrina alkaloids[86] Erysodine, erythroidine [86]
Phenanthrene derivatives [82] Atherosperminine [82][92]
Protopines [82] Protopine, oxomuramine, corycavidine [95]
Aristolactam [82] Doriflavin [82]
Oxazole derivatives[104]
 
 Tyrosine → tyramine[105] Annuloline, halfordinol, texaline, texamine[106]
Isoxazole derivatives
 
 Ibotenic acid → Muscimol Ibotenic acid, Muscimol
Thiazole derivatives[107]
 
 1-Deoxy-D-xylulose 5-phosphate (DOXP), tyrosine, cysteine[108] Nostocyclamide, thiostreptone [107][109]
Quinazoline derivatives[110]
 
 3,4-Dihydro-4-quinazolone derivatives Anthranilic acid or phenylalanine or ornithine[111] Febrifugine[112]
1,4-Dihydro-4-quinazolone derivatives Glycorine, arborine, glycosminine[112]
Pyrrolidine and piperidine quinazoline derivatives Vazicine (peganine) [104]
Acridine derivatives[104]
 
 Anthranilic acid[113] Rutacridone, acronicine[114][115]
Quinoline derivatives[116][117]
 
 Simple derivatives of quinoline derivatives of 2–quinolones and 4-quinolone Anthranilic acid → 3-carboxyquinoline [118] Cusparine, echinopsine, evocarpine[117][119][120]
Tricyclic terpenoids Flindersine[117][121]
Furanoquinoline derivatives Dictamnine, fagarine, skimmianine[117][122][123]
Quinines Tryptophan → tryptamine → strictosidine (with secologanin) → korinanteal → cinhoninon[84][118] Quinine, quinidine, cinchonine, cinhonidine [121]
Indole derivatives[99]
 
See also: indole alkaloids
 Non-isoprene indole alkaloids
Simple indole derivatives [124] Tryptophan → tryptamine or 5-Hydroxytryptophan[125] Serotonin, psilocybin, dimethyltryptamine (DMT), bufotenin[126][127]
Simple derivatives of β-carboline[128] Harman, harmine, harmaline, eleagnine [124]
Pyrroloindole alkaloids [129] Physostigmine (eserine), etheramine, physovenine, eptastigmine[129]
Semiterpenoid indole alkaloids
Ergot alkaloids[99] Tryptophan → chanoclavine → agroclavine → elimoclavine → paspalic acid → lysergic acid[129] Ergotamine, ergobasine, ergosine[130]
Monoterpenoid indole alkaloids
Corynanthe type alkaloids[125] Tryptophan → tryptamine → strictosidine (with secologanin) [125] Ajmalicine, sarpagine, vobasine, ajmaline, yohimbine, reserpine, mitragynine,[131][132] group strychnine and (Strychnine brucine, aquamicine, vomicine[133])
Iboga-type alkaloids[125] Ibogamine, ibogaine, voacangine[125]
Aspidosperma-type alkaloids[125] Vincamine, vinca alkaloids,[26][134] vincotine, aspidospermine[135][136]
Imidazole derivatives[104]
 
 Directly from histidine[137] Histamine, pilocarpine, pilosine, stevensine[104][137]
Purine derivatives[138]
 
 Xanthosine (formed in purine biosynthesis) → 7 methylxantosine → 7-methylxanthine → theobromine → caffeine[84] Caffeine, theobromine, theophylline, saxitoxin[139][140]
Alkaloids with nitrogen in the side chain (protoalkaloids)
β-Phenylethylamine derivatives[91]
 
 Tyrosine or phenylalanine → dioxyphenilalanine → dopamine → adrenaline and mescaline tyrosine → tyramine phenylalanine → 1-phenylpropane-1,2-dione → cathinone → ephedrine and pseudoephedrine[20][51][141] Tyramine, ephedrine, pseudoephedrine, mescaline, cathinone, catecholamines (adrenaline, noradrenaline, dopamine)[20][142]
Colchicine alkaloids [143]
 
 Tyrosine or phenylalanine → dopamine → autumnaline → colchicine[144] Colchicine, colchamine[143]
Muscarine[145]
 
 Glutamic acid → 3-ketoglutamic acid → muscarine (with pyruvic acid)[146] Muscarine, allomuscarine, epimuscarine, epiallomuscarine[145]
Benzylamine[147]
 
 Phenylalanine with valine, leucine or isoleucine[148] Capsaicin, dihydrocapsaicin, nordihydrocapsaicin, vanillylamine[147][149]
Polyamines alkaloids
Putrescine derivatives[150]
 
 ornithine → putrescine → spermidine → spermine[151] Paucine [150]
Spermidine derivatives[150]
 
 Lunarine, codonocarpine[150]
Spermine derivatives[150]
 
 Verbascenine, aphelandrine [150]
Peptide (cyclopeptide) alkaloids
Peptide alkaloids with a 13-membered cycle [47][152] Nummularine C type From different amino acids [47] Nummularine C, Nummularine S [47]
Ziziphine type Ziziphine A, sativanine H [47]
Peptide alkaloids with a 14-membered cycle [47][152] Frangulanine type Frangulanine, scutianine J [152]
Scutianine A type Scutianine A [47]
Integerrine type Integerrine, discarine D [152]
Amphibine F type Amphibine F, spinanine A [47]
Amfibine B type Amphibine B, lotusine C [47]
Peptide alkaloids with a 15-membered cycle [152] Mucronine A type Mucronine A [44][152]
Pseudoalkaloids (terpenes and steroids)
Diterpenes [44]
 
 Lycoctonine type Mevalonic acid → Isopentenyl pyrophosphate → geranyl pyrophosphate[153][154] Aconitine, delphinine[44][155]
Steroidal alkaloids [156]
 
 Cholesterol, arginine[157] Solanidine, cyclopamine, batrachotoxin[158]

Properties

 
Head of a lamb born by a sheep that ate leaves of the corn lily plant. The cyclopia is induced by the cyclopamine present in the plant.

Most alkaloids contain oxygen in their molecular structure; those compounds are usually colorless crystals at ambient conditions. Oxygen-free alkaloids, such as nicotine[159] or coniine,[35] are typically volatile, colorless, oily liquids.[160] Some alkaloids are colored, like berberine (yellow) and sanguinarine (orange).[160]

Most alkaloids are weak bases, but some, such as theobromine and theophylline, are amphoteric.[161] Many alkaloids dissolve poorly in water but readily dissolve in organic solvents, such as diethyl ether, chloroform or 1,2-dichloroethane. Caffeine,[162] cocaine,[163] codeine[164] and nicotine[165] are slightly soluble in water (with a solubility of ≥1g/L), whereas others, including morphine[166] and yohimbine[167] are very slightly water-soluble (0.1–1 g/L). Alkaloids and acids form salts of various strengths. These salts are usually freely soluble in water and ethanol and poorly soluble in most organic solvents. Exceptions include scopolamine hydrobromide, which is soluble in organic solvents, and the water-soluble quinine sulfate.[160]

Most alkaloids have a bitter taste or are poisonous when ingested. Alkaloid production in plants appeared to have evolved in response to feeding by herbivorous animals; however, some animals have evolved the ability to detoxify alkaloids.[168] Some alkaloids can produce developmental defects in the offspring of animals that consume but cannot detoxify the alkaloids. One example is the alkaloid cyclopamine, produced in the leaves of corn lily. During the 1950s, up to 25% of lambs born by sheep that had grazed on corn lily had serious facial deformations. These ranged from deformed jaws to cyclopia (see picture). After decades of research, in the 1980s, the compound responsible for these deformities was identified as the alkaloid 11-deoxyjervine, later renamed to cyclopamine.[169]

Distribution in nature

 
Strychnine tree. Its seeds are rich in strychnine and brucine.

Alkaloids are generated by various living organisms, especially by higher plants – about 10 to 25% of those contain alkaloids.[170][171] Therefore, in the past the term "alkaloid" was associated with plants.[172]

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 (for example, black henbane), fruits or seeds (Strychnine tree), root (Rauvolfia serpentina) or bark (cinchona).[173] Furthermore, different tissues of the same plants may contain different alkaloids.[174]

Beside plants, alkaloids are found in certain types of fungus, such as psilocybin in the fruiting bodies of the genus Psilocybe, and in animals, such as bufotenin in the skin of some toads [23] and a number of insects, markedly ants.[175] Many marine organisms also contain alkaloids.[176] Some amines, such as adrenaline and serotonin, which play an important role in higher animals, are similar to alkaloids in their structure and biosynthesis and are sometimes called alkaloids.[177]

Extraction

 
Crystals of piperine extracted from black pepper.

Because of the structural diversity of alkaloids, there is no single method of their extraction from natural raw materials.[178] Most methods exploit the property of most alkaloids to be soluble in organic solvents [7] but not in water, and the opposite tendency of their salts.

Most plants contain several alkaloids. Their mixture is extracted first and then individual alkaloids are separated.[179] Plants are thoroughly ground before extraction.[178][180] Most alkaloids are present in the raw plants in the form of salts of organic acids.[178] The extracted alkaloids may remain salts or change into bases.[179] 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 that 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 that 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 purified as described above.[178][181]

Alkaloids are separated from their mixture using their different solubility in certain solvents and different reactivity with certain reagents or by distillation.[182]

A number of alkaloids are identified from insects, among which the fire ant venom alkaloids known as solenopsins have received greater attention from researchers.[183] These insect alkaloids can be efficiently extracted by solvent immersion of live fire ants [7] or by centrifugation of live ants [184] followed by silica-gel chromatography purification.[185] Tracking and dosing the extracted solenopsin ant alkaloids has been described as possible based on their absorbance peak around 232 nanometers.[186]

Biosynthesis

Biological precursors of most alkaloids are amino acids, such as ornithine, lysine, phenylalanine, tyrosine, tryptophan, histidine, aspartic acid, and anthranilic acid.[187] Nicotinic acid can be synthesized from tryptophan or aspartic acid. Ways of alkaloid biosynthesis are too numerous and cannot be easily classified.[84] However, there are a few typical reactions involved in the biosynthesis of various classes of alkaloids, including synthesis of Schiff bases and Mannich reaction.[187]

Synthesis of Schiff bases

Main article: Schiff base

Schiff bases can be obtained by reacting amines with ketones or aldehydes.[188] These reactions are a common method of producing C=N bonds.[189]

 

In the biosynthesis of alkaloids, such reactions may take place within a molecule,[187] such as in the synthesis of piperidine:[40]

 

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, which plays the role of the nucleophile in the nucleophilic addition to the ion formed by the reaction of the amine and the carbonyl.[189]

 

The Mannich reaction can proceed both intermolecularly and intramolecularly:[190][191]

 

Dimer alkaloids

In addition to the described above monomeric alkaloids, there are also 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:[192]

There are also dimeric alkaloids formed from two distinct monomers, such as the vinca alkaloids vinblastine and vincristine,[26][134] which are formed from the coupling of catharanthine and vindoline.[193][194] The newer semi-synthetic chemotherapeutic agent vinorelbine is used in the treatment of non-small-cell lung cancer.[134][195] It is another derivative dimer of vindoline and catharanthine and is synthesised from anhydrovinblastine,[196] starting either from leurosine[197][198] or the monomers themselves.[134][194]

 

Biological role

Alkaloids are among the most important and best-known secondary metabolites, i.e. biogenic substances not directly involved in the normal growth, development, or reproduction of the organism. Instead, they generally mediate ecological interactions, which may produce a selective advantage for the organism by increasing its survivability or fecundity. In some cases their function, if any, remains unclear.[199] An early hypothesis, that alkaloids are the final products of nitrogen metabolism in plants, as urea and uric acid are in mammals, was refuted by the finding that their concentration fluctuates rather than steadily increasing.[16]

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, the presence of alkaloids in the plant prevents insects and chordate animals from eating it. However, some animals are adapted to alkaloids and even use them in their own metabolism.[200] Such alkaloid-related substances as serotonin, dopamine and histamine are important neurotransmitters in animals. Alkaloids are also known to regulate plant growth.[201] One example of an organism that uses alkaloids for protection is the Utetheisa ornatrix, more commonly known as the ornate moth. Pyrrolizidine alkaloids render these larvae and adult moths unpalatable to many of their natural enemies like coccinelid beetles, green lacewings, insectivorous hemiptera and insectivorous bats.[202] Another example of alkaloids being utilized occurs in the poison hemlock moth (Agonopterix alstroemeriana). This moth feeds on its highly toxic and alkaloid-rich host plant poison hemlock (Conium maculatum) during its larval stage. A. alstroemeriana may benefit twofold from the toxicity of the naturally-occurring alkaloids, both through the unpalatability of the species to predators and through the ability of A. alstroemeriana to recognize Conium maculatum as the correct location for oviposition.[203] A fire ant venom alkaloid known as solenopsin has been demonstrated to protect queens of invasive fire ants during the foundation of new nests, thus playing a central role in the spread of this pest ant species around the world.[204]

Applications

In medicine

Medical use of alkaloid-containing plants has a long history, and, thus, when the first alkaloids were isolated in the 19th century, they immediately found application in clinical practice.[205] Many alkaloids are still used in medicine, usually in the form of salts widely used including the following:[16][206]

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.[207] For example, naloxone, an opioid receptor antagonist, is a derivative of thebaine that is present in opium.[208]

In agriculture

Prior to the development of a wide range of relatively low-toxic synthetic pesticides, some alkaloids, such as salts of nicotine and anabasine, were used as insecticides. Their use was limited by their high toxicity to humans.[209]

Use as psychoactive drugs

Preparations of plants containing alkaloids and their extracts, and later pure alkaloids, have long been used as psychoactive substances. Cocaine, caffeine, and cathinone are stimulants of the central nervous system.[210][211] Mescaline and many indole alkaloids (such as psilocybin, dimethyltryptamine and ibogaine) have hallucinogenic effect.[212][213] Morphine and codeine are strong narcotic pain killers.[214]

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 and methamphetamine.[215] Thebaine is used in the synthesis of many painkillers such as oxycodone.

See also

Explanatory notes

  1. ^ In the penultimate sentence of his article, W. Meissner (1819) "Über Pflanzenalkalien: II. Über ein neues Pflanzenalkali (Alkaloid)" (On plant alkalis: II. On a new plant alkali (alkaloid)), Journal für Chemie und Physik, 25 : 379–381 ; available on-line at: Hathi Trust – 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." (I.e., "In general, it seems appropriate to me to impose on the currently 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) but follow 'Alkalien']".)

Citations

  1. ^ Andreas Luch (2009). Molecular, clinical and environmental toxicology. Springer. p. 20. ISBN 978-3-7643-8335-0.
  2. ^ a b IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "alkaloids". doi:10.1351/goldbook.A00220
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General and cited references

  • Aniszewski, Tadeusz (2007). Alkaloids: secrets of life. Amsterdam: Elsevier. ISBN 978-0-444-52736-3.
  • Begley, Tadhg P. (2009). Encyclopedia of Chemical Biology. ChemBioChem. Vol. 10. Wiley. pp. 1569–1570. doi:10.1002/cbic.200900262. ISBN 978-0-471-75477-0.
  • Brossi, Arnold (1989). The Alkaloids: Chemistry and Pharmacology. Academic Press.
  • Dewick, Paul M. (2002). Medicinal Natural Products: A Biosynthetic Approach (Second ed.). Wiley. ISBN 978-0-471-49640-3.
  • Fattorusso, E.; Taglialatela-Scafati, O. (2008). Modern Alkaloids: Structure, Isolation, Synthesis and Biology. Wiley-VCH. ISBN 978-3-527-31521-5.
  • Grinkevich NI; Safronich LN, eds. (1983). The chemical analysis of medicinal plants (in Russian). Moscow: Vysshaya Shkola.
  • Hesse, Manfred (2002). Alkaloids: Nature's Curse or Blessing?. Wiley-VCH. ISBN 978-3-906390-24-6.
  • Knunyants, IL (1988). Chemical Encyclopedia. Soviet Encyclopedia.
  • Orekhov, AP (1955). Chemistry alkaloids (Acad. 2nd ed.). Moscow.
  • Plemenkov, VV (2001). Introduction to the Chemistry of Natural Compounds. Kazan.
  • Saxton, J. E. (1971). The Alkaloids: A Specialist Periodical Report. London: The Chemical Society.
  • Veselovskaya, N. B.; Kovalenko, A. E. (2000). Drugs. Moscow: Triada-X.
  • Wink, M (2009). "Mode of action and toxicology of plant toxins and poisonous plants". Mitt. Julius Kühn-Inst. 421: 93–112x.

External links

  •   Media related to Alkaloids at Wikimedia Commons
  •   Quotations related to Alkaloid at Wikiquote

April 30, 2023
alkaloid, this, article, about, class, chemical, compounds, pharmaceutical, company, company, class, basic, naturally, occurring, organic, compounds, that, contain, least, nitrogen, atom, this, group, also, includes, some, related, compounds, with, neutral, ev. This article is about the class of chemical compounds For the pharmaceutical company see Alkaloid company Alkaloids are a class of basic naturally occurring organic compounds that contain at least one nitrogen atom This group also includes some related compounds with neutral 2 and even weakly acidic properties 3 Some synthetic compounds of similar structure may also be termed alkaloids 4 In addition to carbon hydrogen and nitrogen alkaloids may also contain oxygen sulfur and more rarely other elements such as chlorine bromine and phosphorus 5 The first individual alkaloid morphine was isolated in 1804 from the opium poppy Papaver somniferum 1 Alkaloids are produced by a large variety of organisms including bacteria fungi plants and animals 6 They can be purified from crude extracts of these organisms by acid base extraction or solvent extractions followed by silica gel column chromatography 7 Alkaloids have a wide range of pharmacological activities including antimalarial e g quinine antiasthma e g ephedrine anticancer e g homoharringtonine 8 cholinomimetic e g galantamine 9 vasodilatory e g vincamine antiarrhythmic e g quinidine analgesic e g morphine 10 antibacterial e g chelerythrine 11 and antihyperglycemic activities e g piperine 12 failed verification Many have found use in traditional or modern medicine or as starting points for drug discovery Other alkaloids possess psychotropic e g psilocin and stimulant activities e g cocaine caffeine nicotine theobromine 13 and have been used in entheogenic rituals or as recreational drugs Alkaloids can be toxic too e g atropine tubocurarine 14 Although alkaloids act on a diversity of metabolic systems in humans and other animals they almost uniformly evoke a bitter taste 15 The boundary between alkaloids and other nitrogen containing natural compounds is not clear cut 16 Compounds like amino acid peptides proteins nucleotides nucleic acid amines and antibiotics are usually not called alkaloids 2 Natural compounds containing nitrogen in the exocyclic position mescaline serotonin dopamine etc are usually classified as amines rather than as alkaloids 17 Some authors however consider alkaloids a special case of amines 18 19 20 Contents 1 Naming 2 History 3 Classifications 4 Properties 5 Distribution in nature 6 Extraction 7 Biosynthesis 7 1 Synthesis of Schiff bases 7 2 Mannich reaction 8 Dimer alkaloids 9 Biological role 10 Applications 10 1 In medicine 10 2 In agriculture 10 3 Use as psychoactive drugs 11 See also 12 Explanatory notes 13 Citations 14 General and cited references 15 External linksNaming Edit The article that introduced the concept of alkaloid The name alkaloids German Alkaloide was introduced in 1819 by the German chemist Carl Friedrich Wilhelm Meissner and is derived from late Latin root alkali and the Greek language suffix oeidhs like nb 1 However the term came into wide use only after the publication of a review article by Oscar Jacobsen in the chemical dictionary of Albert Ladenburg in the 1880s 21 22 There is no unique method for naming alkaloids 23 Many individual names are formed by adding the suffix ine to the species or genus name 24 For example atropine is isolated from the plant Atropa belladonna strychnine is obtained from the seed of the Strychnine tree Strychnos nux vomica L 5 Where several alkaloids are extracted from one plant their names are often distinguished by variations in the suffix idine anine aline inine etc There are also at least 86 alkaloids whose names contain the root vin because they are extracted from vinca plants such as Vinca rosea Catharanthus roseus 25 these are called vinca alkaloids 26 27 28 History Edit Friedrich Serturner the German chemist who first isolated morphine from opium Alkaloid containing plants have been used by humans since ancient times for therapeutic and recreational purposes For example medicinal plants have been known in Mesopotamia from about 2000 BC 29 The Odyssey of Homer 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 30 A Chinese book on houseplants written in 1st 3rd centuries BC mentioned a medical use of ephedra and opium poppies 31 Also coca leaves have been used by Indigenous South Americans since ancient times 32 Extracts from plants containing toxic alkaloids such as aconitine and tubocurarine were used since antiquity for poisoning arrows 29 Studies of alkaloids began in the 19th century In 1804 the German chemist Friedrich Serturner isolated from opium a soporific principle Latin principium somniferum which he called morphium referring to Morpheus the Greek 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 A significant contribution to the chemistry of alkaloids in the early years of its development was made by the French researchers Pierre Joseph Pelletier and Joseph Bienaime 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 33 The development of the chemistry of alkaloids was accelerated by the emergence of spectroscopic and chromatographic methods in the 20th century so that by 2008 more than 12 000 alkaloids had been identified 34 The first complete synthesis of an alkaloid was achieved in 1886 by the German chemist Albert Ladenburg He produced coniine by reacting 2 methylpyridine with acetaldehyde and reducing the resulting 2 propenyl pyridine with sodium 35 36 Bufotenin an alkaloid from some toads contains an indole core and is produced in living organisms from the amino acid tryptophan Classifications Edit The nicotine molecule contains both pyridine left and pyrrolidine rings right Compared with most other classes of natural compounds alkaloids are characterized by a great structural diversity There is no uniform classification 37 Initially when knowledge of chemical structures was lacking botanical classification of the source plants was relied on This classification is now considered obsolete 5 38 More recent classifications are based on similarity of the carbon skeleton e g indole isoquinoline and pyridine like or biochemical precursor ornithine lysine tyrosine tryptophan etc 5 However they require compromises in borderline cases 37 for example nicotine contains a pyridine fragment from nicotinamide and a pyrrolidine part from ornithine 39 and therefore can be assigned to both classes 40 Alkaloids are often divided into the following major groups 41 True alkaloids contain nitrogen in the heterocycle and originate from amino acids 42 Their characteristic examples are atropine nicotine and morphine This group also includes some alkaloids that besides the nitrogen heterocycle contain terpene e g evonine 43 or peptide fragments e g ergotamine 44 The piperidine alkaloids coniine and coniceine may be regarded as true alkaloids rather than pseudoalkaloids see below 45 although they do not originate from amino acids 46 Protoalkaloids which contain nitrogen but not the nitrogen heterocycle and also originate from amino acids 42 Examples include mescaline adrenaline and ephedrine Polyamine alkaloids derivatives of putrescine spermidine and spermine Peptide and cyclopeptide alkaloids 47 Pseudoalkaloids alkaloid like compounds that do not originate from amino acids 48 This group includes terpene like and steroid like alkaloids 49 as well as purine like alkaloids such as caffeine theobromine theacrine and theophylline 50 Some authors classify ephedrine and cathinone as pseudoalkaloids Those originate from the amino acid phenylalanine but acquire their nitrogen atom not from the amino acid but through transamination 50 51 Some alkaloids do not have the carbon skeleton characteristic of their group So galanthamine and homoaporphines do not contain isoquinoline fragment but are in general attributed to isoquinoline alkaloids 52 Main classes of monomeric alkaloids are listed in the table below Class Major groups Main synthesis steps ExamplesAlkaloids with nitrogen heterocycles true alkaloids Pyrrolidine derivatives 53 Ornithine or arginine putrescine N methylputrescine N methyl D1 pyrroline 54 Cuscohygrine hygrine hygroline stachydrine 53 55 Tropane derivatives 56 Atropine groupSubstitution in positions 3 6 or 7 Ornithine or arginine putrescine N methylputrescine N methyl D1 pyrroline 54 Atropine scopolamine hyoscyamine 53 56 57 Cocaine group Substitution in positions 2 and 3 Cocaine ecgonine 56 58 Pyrrolizidine derivatives 59 Non esters In plants ornithine or arginine putrescine homospermidine retronecine 54 Retronecine heliotridine laburnine 59 60 Complex esters of monocarboxylic acids Indicine lindelophin sarracine 59 Macrocyclic diesters Platyphylline trichodesmine 59 1 aminopyrrolizidines lolines In fungi L proline L homoserine N 3 amino 3 carboxypropyl proline norloline 61 62 Loline N formylloline N acetylloline 63 Piperidine derivatives 64 Lysine cadaverine D1 piperideine 65 Sedamine lobeline anaferine piperine 45 66 Octanoic acid coniceine coniine 46 Coniine coniceine 46 Quinolizidine derivatives 67 68 Lupinine group Lysine cadaverine D1 piperideine 69 Lupinine nupharidin 67 Cytisine group Cytisine 67 Sparteine group Sparteine lupanine anahygrine 67 Matrine group Matrine oxymatrine allomatridine 67 70 71 Ormosanine group Ormosanine piptantine 67 72 Indolizidine derivatives 73 Lysine d semialdehyde of a aminoadipic acid pipecolic acid 1 indolizidinone 74 Swainsonine castanospermine 75 Pyridine derivatives 76 77 Simple derivatives of pyridine Nicotinic acid dihydronicotinic acid 1 2 dihydropyridine 78 Trigonelline ricinine arecoline 76 79 Polycyclic noncondensing pyridine derivatives Nicotine nornicotine anabasine anatabine 76 79 Polycyclic condensed pyridine derivatives Actinidine gentianine pediculinine 80 Sesquiterpene pyridine derivatives Nicotinic acid isoleucine 20 Evonine hippocrateine triptonine 77 78 Isoquinoline derivatives and related alkaloids 81 Simple derivatives of isoquinoline 82 Tyrosine or phenylalanine dopamine or tyramine for alkaloids Amarillis 83 84 Salsoline lophocerine 81 82 Derivatives of 1 and 3 isoquinolines 85 N methylcoridaldine noroxyhydrastinine 85 Derivatives of 1 and 4 phenyltetrahydroisoquinolines 82 Cryptostilin 82 86 Derivatives of 5 naftil isoquinoline 87 Ancistrocladine 87 Derivatives of 1 and 2 benzyl izoquinolines 88 Papaverine laudanosine sendaverineCularine group 89 Cularine yagonine 89 Pavines and isopavines 90 Argemonine amurensine 90 Benzopyrrocolines 91 Cryptaustoline 82 Protoberberines 82 Berberine canadine ophiocarpine mecambridine corydaline 92 Phthalidisoquinolines 82 Hydrastine narcotine Noscapine 93 Spirobenzylisoquinolines 82 Fumaricine 90 Ipecacuanha alkaloids 94 Emetine protoemetine ipecoside 94 Benzophenanthridines 82 Sanguinarine oxynitidine corynoloxine 95 Aporphines 82 Glaucine coridine liriodenine 96 Proaporphines 82 Pronuciferine glaziovine 82 91 Homoaporphines 97 Kreysiginine multifloramine 97 Homoproaporphines 97 Bulbocodine 89 Morphines 98 Morphine codeine thebaine sinomenine 99 Homomorphines 100 Kreysiginine androcymbine 98 Tropoloisoquinolines 82 Imerubrine 82 Azofluoranthenes 82 Rufescine imeluteine 101 Amaryllis alkaloids 102 Lycorine ambelline tazettine galantamine montanine 103 Erythrina alkaloids 86 Erysodine erythroidine 86 Phenanthrene derivatives 82 Atherosperminine 82 92 Protopines 82 Protopine oxomuramine corycavidine 95 Aristolactam 82 Doriflavin 82 Oxazole derivatives 104 Tyrosine tyramine 105 Annuloline halfordinol texaline texamine 106 Isoxazole derivatives Ibotenic acid Muscimol Ibotenic acid MuscimolThiazole derivatives 107 1 Deoxy D xylulose 5 phosphate DOXP tyrosine cysteine 108 Nostocyclamide thiostreptone 107 109 Quinazoline derivatives 110 3 4 Dihydro 4 quinazolone derivatives Anthranilic acid or phenylalanine or ornithine 111 Febrifugine 112 1 4 Dihydro 4 quinazolone derivatives Glycorine arborine glycosminine 112 Pyrrolidine and piperidine quinazoline derivatives Vazicine peganine 104 Acridine derivatives 104 Anthranilic acid 113 Rutacridone acronicine 114 115 Quinoline derivatives 116 117 Simple derivatives of quinoline derivatives of 2 quinolones and 4 quinolone Anthranilic acid 3 carboxyquinoline 118 Cusparine echinopsine evocarpine 117 119 120 Tricyclic terpenoids Flindersine 117 121 Furanoquinoline derivatives Dictamnine fagarine skimmianine 117 122 123 Quinines Tryptophan tryptamine strictosidine with secologanin korinanteal cinhoninon 84 118 Quinine quinidine cinchonine cinhonidine 121 Indole derivatives 99 See also indole alkaloids Non isoprene indole alkaloidsSimple indole derivatives 124 Tryptophan tryptamine or 5 Hydroxytryptophan 125 Serotonin psilocybin dimethyltryptamine DMT bufotenin 126 127 Simple derivatives of b carboline 128 Harman harmine harmaline eleagnine 124 Pyrroloindole alkaloids 129 Physostigmine eserine etheramine physovenine eptastigmine 129 Semiterpenoid indole alkaloidsErgot alkaloids 99 Tryptophan chanoclavine agroclavine elimoclavine paspalic acid lysergic acid 129 Ergotamine ergobasine ergosine 130 Monoterpenoid indole alkaloidsCorynanthe type alkaloids 125 Tryptophan tryptamine strictosidine with secologanin 125 Ajmalicine sarpagine vobasine ajmaline yohimbine reserpine mitragynine 131 132 group strychnine and Strychnine brucine aquamicine vomicine 133 Iboga type alkaloids 125 Ibogamine ibogaine voacangine 125 Aspidosperma type alkaloids 125 Vincamine vinca alkaloids 26 134 vincotine aspidospermine 135 136 Imidazole derivatives 104 Directly from histidine 137 Histamine pilocarpine pilosine stevensine 104 137 Purine derivatives 138 Xanthosine formed in purine biosynthesis 7 methylxantosine 7 methylxanthine theobromine caffeine 84 Caffeine theobromine theophylline saxitoxin 139 140 Alkaloids with nitrogen in the side chain protoalkaloids b Phenylethylamine derivatives 91 Tyrosine or phenylalanine dioxyphenilalanine dopamine adrenaline and mescaline tyrosine tyramine phenylalanine 1 phenylpropane 1 2 dione cathinone ephedrine and pseudoephedrine 20 51 141 Tyramine ephedrine pseudoephedrine mescaline cathinone catecholamines adrenaline noradrenaline dopamine 20 142 Colchicine alkaloids 143 Tyrosine or phenylalanine dopamine autumnaline colchicine 144 Colchicine colchamine 143 Muscarine 145 Glutamic acid 3 ketoglutamic acid muscarine with pyruvic acid 146 Muscarine allomuscarine epimuscarine epiallomuscarine 145 Benzylamine 147 Phenylalanine with valine leucine or isoleucine 148 Capsaicin dihydrocapsaicin nordihydrocapsaicin vanillylamine 147 149 Polyamines alkaloidsPutrescine derivatives 150 ornithine putrescine spermidine spermine 151 Paucine 150 Spermidine derivatives 150 Lunarine codonocarpine 150 Spermine derivatives 150 Verbascenine aphelandrine 150 Peptide cyclopeptide alkaloidsPeptide alkaloids with a 13 membered cycle 47 152 Nummularine C type From different amino acids 47 Nummularine C Nummularine S 47 Ziziphine type Ziziphine A sativanine H 47 Peptide alkaloids with a 14 membered cycle 47 152 Frangulanine type Frangulanine scutianine J 152 Scutianine A type Scutianine A 47 Integerrine type Integerrine discarine D 152 Amphibine F type Amphibine F spinanine A 47 Amfibine B type Amphibine B lotusine C 47 Peptide alkaloids with a 15 membered cycle 152 Mucronine A type Mucronine A 44 152 Pseudoalkaloids terpenes and steroids Diterpenes 44 Lycoctonine type Mevalonic acid Isopentenyl pyrophosphate geranyl pyrophosphate 153 154 Aconitine delphinine 44 155 Steroidal alkaloids 156 Cholesterol arginine 157 Solanidine cyclopamine batrachotoxin 158 Properties Edit Head of a lamb born by a sheep that ate leaves of the corn lily plant The cyclopia is induced by the cyclopamine present in the plant Most alkaloids contain oxygen in their molecular structure those compounds are usually colorless crystals at ambient conditions Oxygen free alkaloids such as nicotine 159 or coniine 35 are typically volatile colorless oily liquids 160 Some alkaloids are colored like berberine yellow and sanguinarine orange 160 Most alkaloids are weak bases but some such as theobromine and theophylline are amphoteric 161 Many alkaloids dissolve poorly in water but readily dissolve in organic solvents such as diethyl ether chloroform or 1 2 dichloroethane Caffeine 162 cocaine 163 codeine 164 and nicotine 165 are slightly soluble in water with a solubility of 1g L whereas others including morphine 166 and yohimbine 167 are very slightly water soluble 0 1 1 g L Alkaloids and acids form salts of various strengths These salts are usually freely soluble in water and ethanol and poorly soluble in most organic solvents Exceptions include scopolamine hydrobromide which is soluble in organic solvents and the water soluble quinine sulfate 160 Most alkaloids have a bitter taste or are poisonous when ingested Alkaloid production in plants appeared to have evolved in response to feeding by herbivorous animals however some animals have evolved the ability to detoxify alkaloids 168 Some alkaloids can produce developmental defects in the offspring of animals that consume but cannot detoxify the alkaloids One example is the alkaloid cyclopamine produced in the leaves of corn lily During the 1950s up to 25 of lambs born by sheep that had grazed on corn lily had serious facial deformations These ranged from deformed jaws to cyclopia see picture After decades of research in the 1980s the compound responsible for these deformities was identified as the alkaloid 11 deoxyjervine later renamed to cyclopamine 169 Distribution in nature Edit Strychnine tree Its seeds are rich in strychnine and brucine Alkaloids are generated by various living organisms especially by higher plants about 10 to 25 of those contain alkaloids 170 171 Therefore in the past the term alkaloid was associated with plants 172 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 for example black henbane fruits or seeds Strychnine tree root Rauvolfia serpentina or bark cinchona 173 Furthermore different tissues of the same plants may contain different alkaloids 174 Beside plants alkaloids are found in certain types of fungus such as psilocybin in the fruiting bodies of the genus Psilocybe and in animals such as bufotenin in the skin of some toads 23 and a number of insects markedly ants 175 Many marine organisms also contain alkaloids 176 Some amines such as adrenaline and serotonin which play an important role in higher animals are similar to alkaloids in their structure and biosynthesis and are sometimes called alkaloids 177 Extraction Edit Crystals of piperine extracted from black pepper Because of the structural diversity of alkaloids there is no single method of their extraction from natural raw materials 178 Most methods exploit the property of most alkaloids to be soluble in organic solvents 7 but not in water and the opposite tendency of their salts Most plants contain several alkaloids Their mixture is extracted first and then individual alkaloids are separated 179 Plants are thoroughly ground before extraction 178 180 Most alkaloids are present in the raw plants in the form of salts of organic acids 178 The extracted alkaloids may remain salts or change into bases 179 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 that 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 that 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 purified as described above 178 181 Alkaloids are separated from their mixture using their different solubility in certain solvents and different reactivity with certain reagents or by distillation 182 A number of alkaloids are identified from insects among which the fire ant venom alkaloids known as solenopsins have received greater attention from researchers 183 These insect alkaloids can be efficiently extracted by solvent immersion of live fire ants 7 or by centrifugation of live ants 184 followed by silica gel chromatography purification 185 Tracking and dosing the extracted solenopsin ant alkaloids has been described as possible based on their absorbance peak around 232 nanometers 186 Biosynthesis EditBiological precursors of most alkaloids are amino acids such as ornithine lysine phenylalanine tyrosine tryptophan histidine aspartic acid and anthranilic acid 187 Nicotinic acid can be synthesized from tryptophan or aspartic acid Ways of alkaloid biosynthesis are too numerous and cannot be easily classified 84 However there are a few typical reactions involved in the biosynthesis of various classes of alkaloids including synthesis of Schiff bases and Mannich reaction 187 Synthesis of Schiff bases Edit Main article Schiff base Schiff bases can be obtained by reacting amines with ketones or aldehydes 188 These reactions are a common method of producing C N bonds 189 In the biosynthesis of alkaloids such reactions may take place within a molecule 187 such as in the synthesis of piperidine 40 Mannich reaction Edit Main article Mannich reaction An integral component of the Mannich reaction in addition to an amine and a carbonyl compound is a 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 189 The Mannich reaction can proceed both intermolecularly and intramolecularly 190 191 Dimer alkaloids EditIn addition to the described above monomeric alkaloids there are also 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 192 Mannich reaction resulting in e g voacamine Michael reaction villalstonine Condensation of aldehydes with amines toxiferine Oxidative addition of phenols dauricine tubocurarine Lactonization carpaine Voacamine Villalstonine Toxiferine Dauricine Tubocurarine CarpaineThere are also dimeric alkaloids formed from two distinct monomers such as the vinca alkaloids vinblastine and vincristine 26 134 which are formed from the coupling of catharanthine and vindoline 193 194 The newer semi synthetic chemotherapeutic agent vinorelbine is used in the treatment of non small cell lung cancer 134 195 It is another derivative dimer of vindoline and catharanthine and is synthesised from anhydrovinblastine 196 starting either from leurosine 197 198 or the monomers themselves 134 194 Biological role EditAlkaloids are among the most important and best known secondary metabolites i e biogenic substances not directly involved in the normal growth development or reproduction of the organism Instead they generally mediate ecological interactions which may produce a selective advantage for the organism by increasing its survivability or fecundity In some cases their function if any remains unclear 199 An early hypothesis that alkaloids are the final products of nitrogen metabolism in plants as urea and uric acid are in mammals was refuted by the finding that their concentration fluctuates rather than steadily increasing 16 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 the presence of alkaloids in the plant prevents insects and chordate animals from eating it However some animals are adapted to alkaloids and even use them in their own metabolism 200 Such alkaloid related substances as serotonin dopamine and histamine are important neurotransmitters in animals Alkaloids are also known to regulate plant growth 201 One example of an organism that uses alkaloids for protection is the Utetheisa ornatrix more commonly known as the ornate moth Pyrrolizidine alkaloids render these larvae and adult moths unpalatable to many of their natural enemies like coccinelid beetles green lacewings insectivorous hemiptera and insectivorous bats 202 Another example of alkaloids being utilized occurs in the poison hemlock moth Agonopterix alstroemeriana This moth feeds on its highly toxic and alkaloid rich host plant poison hemlock Conium maculatum during its larval stage A alstroemeriana may benefit twofold from the toxicity of the naturally occurring alkaloids both through the unpalatability of the species to predators and through the ability of A alstroemeriana to recognize Conium maculatum as the correct location for oviposition 203 A fire ant venom alkaloid known as solenopsin has been demonstrated to protect queens of invasive fire ants during the foundation of new nests thus playing a central role in the spread of this pest ant species around the world 204 Applications EditIn medicine Edit Medical use of alkaloid containing plants has a long history and thus when the first alkaloids were isolated in the 19th century they immediately found application in clinical practice 205 Many alkaloids are still used in medicine usually in the form of salts widely used including the following 16 206 Alkaloid ActionAjmaline antiarrhythmicEmetine antiprotozoal agent EmesisErgot alkaloids Vasoconstriction hallucinogenic UterotonicGlaucine AntitussiveMorphine AnalgesicNicotine Stimulant nicotinic acetylcholine receptor agonistPhysostigmine inhibitor of acetylcholinesteraseQuinidine AntiarrhythmicQuinine Antipyretic antimalarialReserpine antihypertensiveTubocurarine Muscle relaxantVinblastine vincristine antitumorVincamine vasodilating antihypertensiveYohimbine stimulant aphrodisiacMany 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 207 For example naloxone an opioid receptor antagonist is a derivative of thebaine that is present in opium 208 Thebaine NaloxoneIn agriculture Edit Prior to the development of a wide range of relatively low toxic synthetic pesticides some alkaloids such as salts of nicotine and anabasine were used as insecticides Their use was limited by their high toxicity to humans 209 Use as psychoactive drugs Edit Preparations of plants containing alkaloids and their extracts and later pure alkaloids have long been used as psychoactive substances Cocaine caffeine and cathinone are stimulants of the central nervous system 210 211 Mescaline and many indole alkaloids such as psilocybin dimethyltryptamine and ibogaine have hallucinogenic effect 212 213 Morphine and codeine are strong narcotic pain killers 214 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 and methamphetamine 215 Thebaine is used in the synthesis of many painkillers such as oxycodone See also EditAmine Base chemistry List of poisonous plants Mayer s reagent Natural products Palau amine Secondary metaboliteExplanatory notes Edit In the penultimate sentence of his article W Meissner 1819 Uber Pflanzenalkalien II Uber ein neues Pflanzenalkali Alkaloid On plant alkalis II On a new plant alkali alkaloid Journal fur Chemie und Physik 25 379 381 available on line at Hathi Trust Meissner wrote Uberhaupt 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 wurden daher in dem Abschnitt der Pflanzenchemie vor den Pflanzensauren ihre Stelle finden I e In general it seems appropriate to me to impose on the currently 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 Saure acid but follow Alkalien Citations Edit Andreas Luch 2009 Molecular clinical and environmental toxicology Springer p 20 ISBN 978 3 7643 8335 0 a b IUPAC Compendium of Chemical Terminology 2nd ed the Gold Book 1997 Online corrected version 2006 alkaloids doi 10 1351 goldbook A00220 R H F Manske The Alkaloids Chemistry and Physiology Volume VIII New York Academic Press 1965 p 673 Robert Alan Lewis Lewis dictionary of toxicology CRC Press 1998 p 51 ISBN 1 56670 223 2 a b c d Chemical Encyclopedia alkaloids xumuk ru Roberts M F Margaret F Wink Michael 1998 Alkaloids Biochemistry Ecology and Medicinal Applications Boston Springer US ISBN 9781475729054 OCLC 851770197 a b c Goncalves Paterson Fox Eduardo Russ Solis Daniel Delazari dos Santos Lucilene Aparecido dos Santos Pinto Jose Roberto Ribeiro da Silva Menegasso Anally Cardoso Maciel Costa Silva Rafael Sergio Palma Mario Correa Bueno Odair de Alcantara Machado Ednildo April 2013 A simple rapid method for the extraction of whole fire ant venom Insecta Formicidae Solenopsis Toxicon 65 5 8 doi 10 1016 j toxicon 2012 12 009 hdl 11449 74946 PMID 23333648 Kittakoop P Mahidol C Ruchirawat S 2014 Alkaloids as important scaffolds in therapeutic drugs for the treatments of cancer tuberculosis and smoking cessation Curr Top Med Chem 14 2 239 252 doi 10 2174 1568026613666131216105049 PMID 24359196 Russo P Frustaci A Del Bufalo A Fini M Cesario A 2013 Multitarget drugs of plants origin acting on Alzheimer s disease Curr Med Chem 20 13 1686 93 doi 10 2174 0929867311320130008 PMID 23410167 Raymond S Sinatra Jonathan S Jahr J Michael Watkins Pitchford 2010 The Essence of Analgesia and Analgesics Cambridge University Press pp 82 90 ISBN 978 1139491983 Cushnie TP Cushnie B Lamb AJ 2014 Alkaloids An overview of their antibacterial antibiotic enhancing and antivirulence activities Int J Antimicrob Agents 44 5 377 386 doi 10 1016 j ijantimicag 2014 06 001 PMID 25130096 Qiu S Sun H Zhang AH Xu HY Yan GL Han Y Wang XJ 2014 Natural alkaloids basic aspects biological roles and future perspectives Chin J Nat Med 12 6 401 406 doi 10 1016 S1875 5364 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vol 1 pp 213 422 a b Hesse p 5 The suffix ine is a Greek feminine patronymic suffix and means daughter of hence for example atropine means daughter of Atropa belladonna Development of Systematic Names for the Simple Alkanes Archived 2012 03 16 at the Wayback Machine yale edu Hesse p 7 a b c van der Heijden Robert Jacobs Denise I Snoeijer Wim Hallard Didier Verpoorte Robert 2004 The Catharanthus alkaloids Pharmacognosy and biotechnology Current Medicinal Chemistry 11 5 607 628 doi 10 2174 0929867043455846 PMID 15032608 Cooper Raymond Deakin Jeffrey John 2016 Africa s gift to the world Botanical Miracles Chemistry of Plants That Changed the World CRC Press pp 46 51 ISBN 9781498704304 Ravina Enrique 2011 Vinca alkaloids The evolution of drug discovery From traditional medicines to modern drugs John Wiley amp Sons pp 157 159 ISBN 9783527326693 a b Aniszewski p 182 Hesse p 338 Hesse p 304 Hesse p 350 Hesse pp 313 316 Begley Natural Products in Plants a b Koniin in the Great Soviet Encyclopedia 1969 1978 in Russian Hesse p 204 a b Hesse p 11 Orekhov p 6 Aniszewski p 109 a b Dewick p 307 Hesse p 12 a b Plemenkov p 223 Aniszewski p 108 a b c d Hesse p 84 a b Hesse p 31 a b c Dewick p 381 a b c d e f g h i Dimitris C Gournelif Gregory G Laskarisb Robert Verpoorte 1997 Cyclopeptide alkaloids Nat Prod Rep 14 1 75 82 doi 10 1039 NP9971400075 PMID 9121730 Aniszewski p 11 Plemenkov p 246 a b Aniszewski p 12 a b Dewick p 382 Hesse pp 44 53 a b c Plemenkov p 224 a b c Aniszewski p 75 Orekhov p 33 a b c Chemical Encyclopedia Tropan alkaloids xumuk ru Hesse p 34 Aniszewski p 27 a b c d Chemical Encyclopedia Pyrrolizidine alkaloids xumuk ru Plemenkov p 229 Blankenship JD Houseknecht JB Pal S Bush LP Grossman RB Schardl CL 2005 Biosynthetic precursors of fungal pyrrolizidines the loline alkaloids ChemBioChem 6 6 1016 1022 doi 10 1002 cbic 200400327 PMID 15861432 S2CID 13461396 Faulkner JR Hussaini SR Blankenship JD Pal S Branan BM 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 PMID 16755627 S2CID 34409048 Schardl CL Grossman RB Nagabhyru P Faulkner JR Mallik UP 2007 Loline alkaloids currencies of mutualism Phytochemistry 68 7 980 996 doi 10 1016 j phytochem 2007 01 010 PMID 17346759 Plemenkov p 225 Aniszewski p 95 Orekhov p 80 a b c d e f Chemical Encyclopedia Quinolizidine alkaloids xumuk ru Saxton Vol 1 p 93 Aniszewski p 98 Saxton Vol 1 p 91 Joseph P Michael 2002 Indolizidine and quinolizidine alkaloids Nat Prod Rep 19 5 458 475 doi 10 1039 b208137g PMID 14620842 Saxton Vol 1 p 92 Dewick p 310 Aniszewski p 96 Aniszewski p 97 a b c Plemenkov p 227 a b Chemical Encyclopedia pyridine alkaloids xumuk ru a b Aniszewski p 107 a b Aniszewski p 85 Plemenkov p 228 a b Hesse p 36 a b c d e f g h i j k l m n o p q r s t Chemical Encyclopedia isoquinoline alkaloids xumuk ru Aniszewski pp 77 78 a b c d Begley Alkaloid Biosynthesis a b Saxton Vol 3 p 122 a b c Hesse p 54 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Proceedings from the First International Conference The Alkaloids Book 56 1950 p 8 ISBN 978 0 12 469556 6 Veselovskaya p 6 Veselovskaya pp 51 52General and cited references EditAniszewski Tadeusz 2007 Alkaloids secrets of life Amsterdam Elsevier ISBN 978 0 444 52736 3 Begley Tadhg P 2009 Encyclopedia of Chemical Biology ChemBioChem Vol 10 Wiley pp 1569 1570 doi 10 1002 cbic 200900262 ISBN 978 0 471 75477 0 Brossi Arnold 1989 The Alkaloids Chemistry and Pharmacology Academic Press Dewick Paul M 2002 Medicinal Natural Products A Biosynthetic Approach Second ed Wiley ISBN 978 0 471 49640 3 Fattorusso E Taglialatela Scafati O 2008 Modern Alkaloids Structure Isolation Synthesis and Biology Wiley VCH ISBN 978 3 527 31521 5 Grinkevich NI Safronich LN eds 1983 The chemical analysis of medicinal plants in Russian Moscow Vysshaya Shkola Hesse Manfred 2002 Alkaloids Nature s Curse or Blessing Wiley VCH ISBN 978 3 906390 24 6 Knunyants IL 1988 Chemical Encyclopedia Soviet Encyclopedia Orekhov AP 1955 Chemistry alkaloids Acad 2nd ed Moscow Plemenkov VV 2001 Introduction to the Chemistry of Natural Compounds Kazan Saxton J E 1971 The Alkaloids A Specialist Periodical Report London The Chemical Society Veselovskaya N B Kovalenko A E 2000 Drugs Moscow Triada X Wink M 2009 Mode of action and toxicology of plant toxins and poisonous plants Mitt Julius Kuhn Inst 421 93 112x External links Edit Media related to Alkaloids at Wikimedia Commons Quotations related to Alkaloid at Wikiquote Retrieved from https en wikipedia org w index php title Alkaloid amp oldid 1145810999, wikipedia, wiki, book, books, library,

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