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Alkaloids are a broad class of natural product that contain at least one nitrogen atom. Some synthetic compounds of similar structure may also be termed alkaloids.
Alkaloids are produced by a large variety of organisms including bacteria, fungus, Medicinal plant, and . (1998). 9781475729054, Springer US. ISBN 9781475729054 They can be purified from crude extracts of these organisms by acid-base extraction, or solvent extractions followed by silica-gel column chromatography. Alkaloids have a wide range of pharmacology activities including antimalarial (e.g. quinine), asthma (e.g. ephedrine), chemotherapy (e.g. homoharringtonine), cholinomimetic (e.g. galantamine), vasodilation (e.g. vincamine), antiarrhythmic (e.g. quinidine), analgesic (e.g. morphine), (2025). 9781139491983, Cambridge University Press. ISBN 9781139491983 antibacterial (e.g. chelerythrine), and anti-diabetic activities (e.g. berberine). 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), and have been used in entheogenic rituals or as recreational drugs. Alkaloids can be toxicity (e.g. atropine, tubocurarine). (1996). 9780683085006, Lippincott, Williams & Wilkins. ISBN 9780683085006 Although alkaloids act on a diversity of metabolic systems in humans and other animals, they almost uniformly evoke a bitter taste.
The boundary between alkaloids and other nitrogen-containing natural compounds is not clear-cut.Robert A. Meyers Encyclopedia of Physical Science and Technology – Alkaloids, 3rd edition. Most alkaloids are basic, although some have neutral and even weakly properties. In addition to carbon, hydrogen and nitrogen, alkaloids may also contain oxygen or sulfur. Rarer still, they may contain elements such as phosphorus, chlorine, and bromine. Compounds like amino acid , , , nucleic acid, , and antibiotics are usually not called alkaloids. Natural compounds containing nitrogen in the exocyclic position (mescaline, serotonin, dopamine, etc.) are usually classified as rather than as alkaloids. Some authors, however, consider alkaloids a special case of amines.Aniszewski, p. 110
There is no unique method for naming alkaloids.Hesse, p. 5 Many individual names are formed by adding the suffix "ine" to the species or genus name.The suffix "ine" is a Greek feminine patronymic suffix and means "daughter of"; hence, for example, "atropine" means "daughter of Atropa" (belladonna): For example, atropine is isolated from the plant Atropa belladonna; strychnine is obtained from the seed of the Strychnine tree ( Strychnos nux-vomica L.). 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);Hesse, p. 7 these are called vinca alkaloid.
Extracts from plants containing toxic alkaloids, such as aconitine and tubocurarine, were used since antiquity for poisoning arrows.
Studies of alkaloids began in the 19th century. In 1804, the German chemist Friedrich Sertürner isolated from opium a "soporific principle" (), 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).Hesse, pp. 313–316 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.Begley, Natural Products in Plants.
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.Hesse, p. 204
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.). However, they require compromises in borderline cases; for example, nicotine contains a pyridine fragment from nicotinamide and a pyrrolidine part from ornithineAniszewski, p. 109 and therefore can be assigned to both classes.Dewick, p. 307
Alkaloids are often divided into the following major groups:Hesse, p. 12
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.Hesse, pp. 44, 53
Main classes of monomeric alkaloids are listed in the table below:
| Alkaloids with nitrogen heterocycles (true alkaloids) | |||
| Pyrrolidine derivativesPlemenkov, p. 224 | Ornithine or arginine → putrescine → N-methylputrescine → N-methyl-Δ1-pyrrolineAniszewski, p. 75 | Cuscohygrine, hygrine, hygroline, stachydrineOrekhov, p. 33 | |
| Tropane derivatives | Atropine group Substitution in positions 3, 6 or 7 | Ornithine or arginine → putrescine → N-methylputrescine → N-methyl-Δ1-pyrroline | Atropine, scopolamine, hyoscyamineHesse, p. 34 |
| Cocaine group Substitution in positions 2 and 3 | Cocaine, ecgonineAniszewski, p. 27 | ||
| Pyrrolizidine derivatives | Non-esters | In plants: ornithine or arginine → putrescine → homospermidine → retronecine | Retronecine, heliotridine, laburninePlemenkov, p. 229 |
| Complex esters of monocarboxylic acids | Indicine, lindelophin, sarracine | ||
| Macrocyclic diesters | Platyphylline, trichodesmine | ||
| 1-aminopyrrolizidines (Loline alkaloids) | In Neotyphodium: Proline + homoserine → N-(3-amino-3-carboxypropyl)proline → norloline | Loline, N-formylloline, N-acetylloline | |
| Piperidine derivativesPlemenkov, p. 225 | Lysine → cadaverine → Δ1-piperideineAniszewski, p. 95 | Sedamine, lobeline, anaferine, piperineOrekhov, p. 80 | |
| Caprylic acid → coniceine → coniine | Coniine, coniceine | ||
| Quinolizidine derivativesSaxton, Vol. 1, p. 93 | Lupinine group | Lysine → cadaverine → Δ1-piperideineAniszewski, p. 98 | Lupinine, nupharidin |
| Cytisine group | Cytisine | ||
| Sparteine group | Sparteine, lupanine, anahygrine | ||
| Matrine group. | Matrine, oxymatrine, allomatridineSaxton, Vol. 1, p. 91 | ||
| Ormosanine group | Ormosanine, piptantineSaxton, Vol. 1, p. 92 | ||
| Indolizidine derivativesDewick, p. 310 | Lysine → δ-semialdehyde of α-aminoadipic acid → pipecolic acid → 1 indolizidinoneAniszewski, p. 96 | Swainsonine, castanospermineAniszewski, p. 97 | |
| Pyridine derivativesPlemenkov, p. 227 | Simple derivatives of pyridine | Nicotinic acid → dihydronicotinic acid → 1,2-dihydropyridineAniszewski, p. 107 | Trigonelline, ricinine, arecolineAniszewski, p. 85 |
| Polycyclic noncondensing pyridine derivatives | Nicotine, nornicotine, anabasine, anatabine | ||
| Polycyclic condensed pyridine derivatives | Actinidine, gentianine, pediculininePlemenkov, p. 228 | ||
| Sesquiterpene pyridine derivatives | Nicotinic acid, isoleucine | Evonine, hippocrateine, triptonine | |
| Isoquinoline derivatives and related alkaloidsHesse, p. 36 | Simple derivatives of isoquinoline | Tyrosine or phenylalanine → dopamine or tyramine (for alkaloids Amarillis)Aniszewski, pp. 77–78Begley, Alkaloid Biosynthesis | Salsoline, lophocerine |
| Derivatives of 1- and 3-isoquinolinesSaxton, Vol. 3, p. 122 | N-methylcoridaldine, noroxyhydrastinine | ||
| Derivatives of 1- and 4-phenyltetrahydroisoquinolines | CryptostilinHesse, p. 54 | ||
| Derivatives of 5-naftil-isoquinolineHesse, p. 37 | Ancistrocladine | ||
| Derivatives of 1- and 2-benzyl-izoquinolinesHesse, p. 38 | Papaverine, laudanosine, sendaverine | ||
| Cularine groupHesse, p. 46 | Cularine, yagonine | ||
| Pavines and isopavinesHesse, p. 50 | Argemonine, amurensine | ||
| Benzopyrrocolines | Cryptaustoline | ||
| Protoberberines | Berberine, canadine, ophiocarpine, mecambridine, corydalineHesse, p. 47 | ||
| Phthalidisoquinolines | Hydrastine, narcotine (Noscapine)Hesse, p. 39 | ||
| Spirobenzylisoquinolines | Fumaricine | ||
| Ipecacuanha alkaloidsHesse, p. 41 | Emetine, protoemetine, ipecoside | ||
| Benzophenanthridines | Sanguinarine, oxynitidine, corynoloxineHesse, p. 49 | ||
| Glaucine, coridine, liriodenineHesse, p. 44 | |||
| Proaporphines | Pronuciferine, glaziovine | ||
| HomoaporphinesSaxton, Vol. 3, p. 164 | Kreysiginine, multifloramine | ||
| Homoproaporphines | Bulbocodine | ||
| Hesse, p. 51 | Morphine, codeine, thebaine, sinomenine,Plemenkov, p. 236 heroin | ||
| HomomorphinesSaxton, Vol. 3, p. 163 | Kreysiginine, androcymbine | ||
| Tropoloisoquinolines | Imerubrine | ||
| Azofluoranthenes | Rufescine, imeluteineSaxton, Vol. 3, p. 168 | ||
| Amaryllis alkaloidsHesse, p. 52 | Lycorine, ambelline, tazettine, galantamine, montanineHesse, p. 53 | ||
| Erythrina alkaloids | Erysodine, erythroidine | ||
| Phenanthrene derivatives | Atherosperminine | ||
| Protopine, oxomuramine, corycavidine | |||
| Aristolactam | Doriflavin | ||
| Oxazole derivativesPlemenkov, p. 241 | Tyrosine → tyramineBrossi, Vol. 35, p. 261 | Annuloline, halfordinol, texaline, texamineBrossi, Vol. 35, pp. 260–263 | |
| Isoxazole derivatives | Ibotenic acid → Muscimol | Ibotenic acid, Muscimol | |
| Thiazole derivativesPlemenkov, p. 242 | 1-Deoxy-D-xylulose 5-phosphate (DOXP), tyrosine, cysteineBegley, Cofactor Biosynthesis | Nostocyclamide, thiostreptone | |
| Quinazoline derivatives | 3,4-Dihydro-4-quinazolone derivatives | Anthranilic acid or phenylalanine or ornithineAniszewski, p. 106 | FebrifugineAniszewski, p. 105 |
| 1,4-Dihydro-4-quinazolone derivatives | Glycorine, arborine, glycosminine | ||
| Pyrrolidine and piperidine quinazoline derivatives | Vazicine (peganine) | ||
| Acridine derivatives | Anthranilic acid | Rutacridone, acronicinePlemenkov, pp. 231, 246Hesse, p. 58 | |
| Quinoline derivativesPlemenkov, p. 231 | Simple derivatives of quinoline derivatives of 2–quinolones and 4-quinolone | Anthranilic acid → 3-carboxyquinolineAniszewski, p. 114 | Cusparine, echinopsine, evocarpineOrekhov, p. 205Hesse, p. 55 |
| Tricyclic terpenoids | FlindersinePlemenkov, p. 232 | ||
| Furanoquinoline derivatives | Dictamnine, fagarine, skimmianineOrekhov, p. 212Aniszewski, p. 118 | ||
| Tryptophan → tryptamine → strictosidine (with secologanin) → korinanteal → cinhoninon | Quinine, quinidine, cinchonine, cinhonidine | ||
| Indole derivatives | Non-isoprene indole alkaloids | ||
| Simple indole derivativesAniszewski, p. 112 | Tryptophan → tryptamine or 5-HydroxytryptophanAniszewski, p. 113 | Serotonin, psilocybin, dimethyltryptamine (DMT), bufoteninHesse, p. 15Saxton, Vol. 1, p. 467 | |
| Simple derivatives of beta-carbolineDewick, pp. 349–350 | Harman, harmine, harmaline, eleagnine | ||
| Pyrroloindole alkaloidsAniszewski, p. 119 | Physostigmine (eserine), etheramine, physovenine, eptastigmine | ||
| Semiterpenoid indole alkaloids | |||
| Ergoline | Tryptophan → chanoclavine → agroclavine → elimoclavine → paspalic acid → lysergic acid | Ergotamine, ergobasine, ergosineHesse, p. 29 | |
| Monoterpenoid indole alkaloids | |||
| Corynanthe type alkaloids | Tryptophan → tryptamine → strictosidine (with secologanin) | Ajmalicine, sarpagine, vobasine, ajmaline, yohimbine, reserpine, mitragynine,Hesse, pp. 23–26Saxton, Vol. 1, p. 169 group strychnine and (Strychnine brucine, aquamicine, vomicineSaxton, Vol. 5, p. 210) | |
| Iboga-type alkaloids | Ibogamine, ibogaine, voacangine | ||
| Aspidosperma-type alkaloids | Vincamine, vinca alkaloid, vincotine, aspidospermineHesse, pp. 17–18Dewick, p. 357 | ||
| Imidazole derivatives | Directly from histidineAniszewski, p. 104 | Histamine, pilocarpine, pilosine, stevensine | |
| Purine derivativesHesse, p. 72 | Xanthosine (formed in purine biosynthesis) → 7 methylxantosine → 7-methylxanthine → theobromine → caffeine | Caffeine, theobromine, theophylline, saxitoxinHesse, p. 73Dewick, p. 396 | |
| Alkaloids with nitrogen in the side chain (protoalkaloids) | |||
| β-Phenylethylamine derivatives | Tyrosine or phenylalanine → dioxyphenilalanine → dopamine → adrenaline and mescaline tyrosine → tyramine phenylalanine → 1-phenylpropane-1,2-dione → cathinone → ephedrine and pseudoephedrine | Tyramine, ephedrine, pseudoephedrine, mescaline, cathinone, catecholamines (adrenaline, noradrenaline, dopamine)Hesse, p. 76 | |
| Colchicine alkaloids | Tyrosine or phenylalanine → dopamine → autumnaline → colchicineAniszewski, p. 77 | Colchicine, colchamine | |
| MuscarineHesse, p. 81 | Glutamic acid → 3-ketoglutamic acid → muscarine (with pyruvic acid)Brossi, Vol. 23, p. 376 | Muscarine, allomuscarine, epimuscarine, epiallomuscarine | |
| BenzylamineHesse, p. 77 | Phenylalanine with valine, leucine or isoleucineBrossi, Vol. 23, p. 268 | Capsaicin, dihydrocapsaicin, nordihydrocapsaicin, vanillylamineBrossi, Vol. 23, p. 231 | |
| Polyamines alkaloids | |||
| Putrescine derivativesHesse, p. 82 | ornithine → putrescine → spermidine → spermine | Paucine | |
| Spermidine derivatives | Lunarine, codonocarpine | ||
| Spermine derivatives | Verbascenine, aphelandrine | ||
| Peptide (cyclopeptide) alkaloids | |||
| Peptide alkaloids with a 13-membered cyclePlemenkov, p. 243 | Nummularine C type | From different amino acids | Nummularine C, Nummularine S |
| Ziziphine type | Ziziphine A, sativanine H | ||
| Peptide alkaloids with a 14-membered cycle | Frangulanine type | Frangulanine, scutianine J | |
| Scutianine A type | Scutianine A | ||
| Integerrine type | Integerrine, discarine D | ||
| Amphibine F type | Amphibine F, spinanine A | ||
| Amfibine B type | Amphibine B, lotusine C | ||
| Peptide alkaloids with a 15-membered cycle | Mucronine A type | Mucronine A | |
| Pseudoalkaloids (terpenes and steroids) | |||
| Diterpenes | Lycoctonine type | Mevalonic acid → Isopentenyl pyrophosphate → geranyl pyrophosphateBegley, Natural Products: An Overview | Aconitine, delphinine |
| Steroidal alkaloidsHesse, p. 88 | Cholesterol, arginineDewick, p. 388 | Solanidine, cyclopamine, batrachotoxinPlemenkov, p. 247 | |
Most alkaloids are weak bases, but some, such as theobromine and theophylline, are amphoteric. Many alkaloids dissolve poorly in water but readily dissolve in , such as diethyl ether, chloroform or 1,2-dichloroethane. Caffeine, cocaine, codeine and nicotine are slightly soluble in water (with a solubility of ≥1g/L), whereas others, including morphine and yohimbine 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.
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.Fattorusso, p. 53 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. After decades of research, in the 1980s, the compound responsible for these deformities was identified as the alkaloid 11-deoxyjervine, later renamed to cyclopamine.
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), or (Strychnine tree), root ( Rauvolfia serpentina) or bark (cinchona).Grinkevich, pp. 122–123 Furthermore, different tissues of the same plants may contain different alkaloids.Orekhov, p. 12
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 and a number of insects, markedly ants. Many marine organisms also contain alkaloids.Fattorusso, p. XVII 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.Aniszewski, pp. 110–111
Most plants contain several alkaloids. Their mixture is extracted first and then individual alkaloids are separated.Grinkevich, p. 132 Plants are thoroughly ground before extraction.Grinkevich, p. 5 Most alkaloids are present in the raw plants in the form of salts of organic acids. The 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 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.Grinkevich, pp. 132–134
Alkaloids are separated from their mixture using their different solubility in certain solvents and different reactivity with certain reagents or by distillation.Grinkevich, pp. 134–136
A number of alkaloids are identified from , among which the fire ant venom alkaloids known as have received greater attention from researchers. These insect alkaloids can be efficiently extracted by solvent immersion of live fire ants or by centrifugation of live ants followed by silica-gel chromatography purification. Tracking and dosing the extracted solenopsin ant alkaloids has been described as possible based on their absorbance peak around 232 nanometers.
In the biosynthesis of alkaloids, such reactions may take place within a molecule, such as in the synthesis of piperidine:
The Mannich reaction can proceed both intermolecularly and intramolecularly:Plemenkov, p. 255Dewick, p. 305
There are also dimeric alkaloids formed from two distinct monomers, such as the vinca alkaloids vinblastine and vincristine, which are formed from the coupling of catharanthine and vindoline. (2025). 9783540728795, Springer Science & Business Media. ISBN 9783540728795 The newer semisynthesis chemotherapeutic agent vinorelbine is used in the treatment of non-small-cell lung cancer. It is another derivative dimer of vindoline and catharanthine and is synthesised from anhydrovinblastine, starting either from leurosine or the monomers themselves.
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.Hesse, pp. 283–291 Such alkaloid-related substances as serotonin, dopamine and histamine are important in animals. Alkaloids are also known to regulate plant growth.Aniszewski, pp. 142–143 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.W.E. Conner (2009). Tiger Moths and Woolly Bears—behaviour, ecology, and evolution of the Arctiidae. New York: Oxford University Press. pp. 1–10. . 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 Conium maculatum ( 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. 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.
| Ajmaline | Antiarrhythmic |
| Emetine | Antiprotozoal agent, emesis |
| Ergoline | Vasoconstriction, Psychedelic drug, Uterotonic |
| Glaucine | Antitussive |
| Morphine | Analgesic |
| Nicotine | Stimulant, nicotinic acetylcholine receptor agonist |
| Physostigmine | Inhibitor of acetylcholinesterase |
| Quinidine | Antiarrhythmic |
| Quinine | Antipyretic, antimalarial |
| Reserpine | Antihypertensive |
| Tubocurarine | Muscle relaxant |
| Vinblastine, vincristine | Chemotherapy |
| Vincamine | Vasodilation, antihypertensive |
| Yohimbine | Stimulant, aphrodisiac |
| Berberine | Antihyperglycaemic |
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.Hesse, p. 309 For example, naloxone, an opioid receptor antagonist, is a derivative of thebaine that is present in opium.Dewick, p. 335
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.Veselovskaya, pp. 51–52 Thebaine is used in the synthesis of many painkillers such as oxycodone.
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