, was isolated in 1804 from poppy (Papaver 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 and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids. In addition to carbon, hydrogen and nitrogen, alkaloids may also contain oxygen, sulfur and more rarely other elements such as chlorine, bromine and phosphorus.

Alkaloids are produced by a large variety of organisms, including bacteria, fungi, plants, and animals and are part of the group of natural products (also called secondary metabolites). Many alkaloids can be purified from crude extracts by acid-base extraction. Many alkaloids are toxic to other organisms. They often have pharmacological effects and are used as medications, as recreational drugs, or in entheogenic rituals. Examples are the local anesthetic and stimulant, cocaine; the stimulant, caffeine; nicotine; the analgesic, morphine; the antibacterial, berberine; the anticancer compound, vincrinstine; the antihypertension agent, resepine; the cholinomimeric, galatamine; the spasmolysis agent, atropine; the vasodilator, vincamine; the anti-arhythmia compound, quinidine; the anti-asthma therapeutic, ephedrine; and the antimalarial drug, quinine. Although alkaloids act on a diversity of metabolic systems in humans and other animals, they almost uniformly invoke a bitter taste.

The boundary between alkaloids and other nitrogen-containing natural compounds is not clear-cut. Compounds like amino acid peptides, proteins, nucleotides, nucleic acid, amines and antibiotics are usually not called alkaloids. Some authors, however, consider alkaloids a special case of amines.

Naming

The name "alkaloids" () was introduced in 1819 by the German chemist Carl F.W. Meissner, and is derived from late Latin root (which, in turn, comes from the Arabic al qualja - "ashes of plants") and the suffix - "like". However, the term came into wide use only after the publication of a review article by O. Jacobsen in the chemical dictionary of Albert Ladenburg in the 1880s.

There is no unique method of naming alkaloids. Many individual names are formed by adding the suffix "-ine" to the species or generic alkaloids. For example, atropine is isolated from the plant Atropa belladonna, strychnine is obtained from the seed of Strychnine tree.

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. 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. A Chinese book on houseplants written in 1st-3rd centuries BC mentioned a medical use of Ephedra and opium poppies. Also, coca leaves were used by South American Indians since ancient times.

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

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. 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.

Classification

, a poison from some toads, contains an indole core and is produced in living organisms from the amino acid tryptophan.]] 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 and there is no uniform classification of alkaloids. 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 knowledge about the chemical structure of alkaloids and is now considered obsolete.

More recent classifications are based on similarity of the carbon skeleton (e.g., indole, isoquinoline and pyridine-like) or biogenetic precursor (ornithine, lysine, tyrosine, tryptophan, etc.). and therefore can be assigned to both classes.

Alkaloids are often divided into the following major groups:

# "True alkaloids", which contain nitrogen in the heterocycle and originate from amino acids. Their characteristic examples are atropine, nicotine and morphine. This group also includes some alkaloids which beside nitrogen heterocycle contain terpene (e.g. evonine) or peptide fragments (e.g. ergotamine). This group also includes piperidine alkaloids coniine and coniceine although they do not originate from amino acids. # "Protoalkaloids", which contain nitrogen and also originate from amino acids. #Pseudalkaloids – alkaloid-like compounds which do not originate from amino acids. This group includes, terpene-like and steroid-like alkaloids, as well as purine-like alkaloids such as caffeine, theobromine and theophylline. Some authors classify as pseudoalkaloids such compounds such as ephedrine and cathinone. Those originate from the amino acid phenylalanine, but acquire their nitrogen atom not from the amino acid but through transamination.

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.

Main classes of monomeric alkaloids are listed in the table below: {| Class = "wikitable" |- ! Class !Major groups !Main synthesis steps !Examples |- | Colspan = "4" align = "center" bgcolor = "# DADADA" |Alkaloids with nitrogen heterocycles (true alkaloids) |- | Pyrrolidine derivatives | | Ornithine or arginine → putrescine → N-methylputrescine → N-methyl-Δ¹-pyrroline | Cuscohygrine, hygrine, hygroline, stachydrine |- | Rowspan = "2"|Tropane derivatives | Atropine groupSubstitution in positions 3, 6 or 7 | Rowspan = "2"|Ornithine or arginine → putrescine → N-methylputrescine → N-methyl-Δ¹-pyrroline |- | Cocaine group Substitution in positions 2 and 3 | Cocaine, ecgonine |- | Rowspan = "4"|Pyrrolizidine derivatives | Non-esters | Rowspan = "3"|In plants: ornithine or arginine → putrescine → homospermidine → retronecine |- | Complex esters of monocarboxylic acids | Indicine, lindelophin, sarracine |Loline, N-formylloline, N-acetylloline |- | Rowspan = "2"|Piperidine derivatives | | Lysine → cadaverine → Δ¹-piperideine | Sedamine, lobeline, anaferine, piperine |- | | Octanoic acid → coniceine → coniine | Lupinine group | Rowspan = "5"|Lysine → cadaverine → Δ¹-piperideine | Lupinine, nupharidin |- | Ormosanine group | Ormosanine, piptantine |- | Indolizidine derivatives | | Lysine → δ-semialdehyde of α-aminoadipic acid → pipecolic acid → 1 indolizidinone | Swainsonine, castanospermine |- | Rowspan = "4"|Pyridine derivatives | Simple derivatives of pyridine | Rowspan = "3"|Nicotinic acid → dihydronicotinic acid → 1,2-dihydropyridine | Trigonelline, ricinine, arecoline |- | Polycyclic noncondensing pyridine derivatives | Nicotine, nornicotine, anabasine, anatabine |- | Sesquiterpene pyridine derivatives | Nicotinic acid, isoleucine | Simple derivatives of isoquinoline | Rowspan = "26"|Tyrosine or phenylalanine → dopamine or tyramine (for alkaloids Amarillis) | Salsoline, lophocerine | N-methylcoridaldine, noroxyhydrastinine |- | Derivatives of 5-naftil-isoquinoline | Ancistrocladine | Papaverine, laudanosine, sendaverine |- | Cularine group | Cularine, yagonine | Argemonine, amurensin | Cryptaustoline |- | Phtalidisoquinolines |- | Spirobenzylisoquinolines | Emetine, protoemetine, ipecoside |- | Aporphines |- | Proaporphines | Kreysiginine, multifloramine | Morphine, codeine, thebaine, sinomenine |- | Homomorphines | Kreysiginine, androcymbine |- | Amaryllis alkaloids | Lycorine, ambelline, tazettine, galantamine, montanine |- | Erythrite alkaloids | | Tyrosine → tyramine | Annuloline, halfordinol, texaline, texamine |- | Isoxazole derivatives | |Ibotenic acid → Muscimol |Ibotenic acid, Muscimol |- | Thiazole derivatives | | 1-Deoxy-D-xylulose 5-phosphate (DOXP), tyrosine, cysteine | Nostocyclamide, thiostreptone |- | Rowspan = "3"|Quinazoline derivatives | 3,4-Dihydro-4-quinazolone derivatives | Rowspan = "3"|Anthranilic acid or phenylalanine or ornithine | Febrifugine |- | 1,4-Dihydro-4-quinazolone derivatives | Glycorine, arborine, glycosminine | Rutacridone, acronicine |- | Rowspan = "4"|Quinoline derivatives | Simple derivatives of quinoline derivatives of 2 - quinolones and 4-quinolone | Rowspan = "3"|Anthranilic acid → 3-carboxyquinoline | Cusparine, echinopsine, evocarpine |- | Tricyclic terpenoids | Flindersine |- | Furanoquinoline derivatives | Dictamnine, fagarine, skimmianine |- | Quinines | Tryptophan → tryptamine → strictosidine (with secologanin) → korinanteal → cinhoninon | Rowspan = "3"|Tryptophan → tryptamine or 5-hydroxitriptofan | Serotonin, psilocybin, dimethyltryptamine (DMT), bufotenin |- | Simple derivatives of β-carboline | Harman, harmine, harmaline, eleagnine | Physostigmine (eserine), etheramine, physovenine, eptastigmine |- | Colspan = "3" align = "center" |Monoterpenoid indole alkaloids |- | Corynanthe type alkaloids group strychnine and (Strychnine brucine, aquamicine, vomicine ) |- | Iboga-type alkaloids |- | Imidazole derivatives | Histamine, pilocarpine, pilosine, stevensine | | Xanthosine (formed in purine biosynthesis) → 7 methylxantosine → 7-methyl xanthine → theobromine → caffeine |- | Colspan = "4" align = "center" bgcolor = "# DADADA" |Alkaloids with nitrogen in the side chain (protoalkaloids) |- | β-Phenylethylamine derivatives | Tyramine, ephedrine, pseudoephedrine, mescaline, cathinone, catecholamines (adrenaline, noradrenaline, dopamine) |- | Colchicine alkaloids | | Tyrosine or phenylalanine → dopamine → autumnaline → colchicine | Colchicine, colchamine | | Glutamic acid → 3-ketoglutamic acid → muscarine (with pyruvic acid) | Muscarine, allomuscarine, epimuscarine, epiallomuscarine | | Phenylalanine with valine, leucine or isoleucine | Capsaicin, dihydrocapsaicin, nordihydrocapsaicin |- | Colspan = "4" align = "center" bgcolor = "# DADADA" |Polyamines alkaloids |- | Putrescine derivatives | | Rowspan = "3"|ornithine → putrescine → spermidine → spermine | Paucine | Numularine C type | Rowspan = "8"|From different amino acids | Aconitine, delphinine |- | Steroids | | Cholesterol, arginine | Solasodine, solanidine, veralkamine |}

Properties

plant. The cyclopia in the calf is induced by the alkaloid cyclopamine present in the plant.]] Most alkaloids contain oxygen; those compounds are usually colorless crystals at ambient conditions. Oxygen-free alkaloids, such as nicotine or coniine, Some alkaloids are colored, like berberine (yellow) and sanguinarine (orange). Most alkaloids are poorly soluble in water but readily dissolve in organic solvents, such as diethyl ether, chloroform and 1,2-dichloroethane. However, caffeine dissolves well in boiling water. 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, which is present in the leaves of corn 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 11-deoxyjervine, which was renamed cyclopamine.

Distribution in nature

. 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. Therefore, in the past the term "alkaloid" was 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 henbane), fruits or seeds (Strychnine tree), root (Rauwolfia serpentina) or bark (cinchona). Furthermore, different tissues of the same plants may contain different alkaloids.

Beside plants, alkaloids are found in certain types of fungi, such as psilocybin in the fungus of the genus Psilocybe, and in animals, such as bufotenin in the skin of some toads. 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.

Extraction

extracted from black pepper.]]

Because of the structural diversity of alkaloids, there is no single method of their extraction from natural raw materials. 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 alkaloids are separated. Plants are thoroughly ground before extraction. Most alkaloids are present in the raw plants in the form of salts of organic acids.

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

Biosynthesis

Biological precursors of most alkaloids are amino acids, such as ornithine, lysine, phenylalanine, tyrosine, tryptophan, histidine, aspartic acid and anthranilic acid. Nicotinic acid can be synthesized from tryptophan or aspartic acid. Ways of alkaloid biosynthesis are too numerous and can not be easily classified. These reactions are a common method of producing C=N bonds.

In the biosynthesis of alkaloids, such reactions may take place within a molecule,

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:

Mannich reaction, resulting in, e.g., voacamine

Michael reaction (villalstonine).

Condensation of aldehydes with amines (toxiferine).

Oxidative addition of phenols (dauricine, tubocurarine).

Lactonization (carpaine).

The biological role

The role of alkaloids for living organisms which produce them is still unclear. Initially it was assumed that the alkaloids are the final products of nitrogen metabolism in plants, and urea in mammals. Later it was shown that alkaloid concentrations varies over time and this hypothesis was refuted. Such alkaloid-related substances as serotonin, dopamine and histamine are important neurotransmitters in animals. Alkaloids are also known to regulate plant growth.

Applications

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. Many alkaloids are still used in medicine, usually in the form of salts, including the following::

{| Class = "wikitable" ! Alkaloid ! Action |- | Ajmaline | antiarrhythmic |- | Atropine, scopolamine, hyoscyamine | anticholinergic |- | Vinblastine, vincristine | antitumor |- | Vincamine | vasodilating, antihypertensive |- | Codeine | cough medicine |- | Cocaine | anesthetic |- | Colchicine | remedy for gout |- | Morphine | analgesic |- | Reserpine | antihypertensive |- | Tubocurarine | Muscle relaxant |- | Physostigmine | inhibitor of acetylcholinesterase |- | Quinidine | antiarrhythmic |- | Quinine | antipyretics, antimalarial |- | Emetine | antiprotozoal agent |- | Ergot alkaloids | sympathomimetic, vasodilator, antihypertensive |}

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. For example, naloxone, an opioid receptor antagonist, is a derivative of thebaine which is present in opium.

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.

Use as psychoactive drugs

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

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.

See also

Amine

Base (chemistry)

Natural products

Secondary metabolite

Notes

References

Bibliography

N. B. Veselovskaya, AE Kovalenko Drugs, M.: Triada-X, 2000

*

Dennis Jon McKenna (born December 17, 1950) is an American ethnopharmacologist, author and brother to well-known psychedelics proponent Terence McKenna.

Profile

McKenna's research led to the development of natural products for Aveda Corporation as well as greater awareness of natural products and medicines. He has authored numerous scientific articles and books. He co-authored The Invisible Landscape with his brother Terence. McKenna spent a number of years as a senior lecturer for the Center for Spirituality and Healing, part of the Academic Health Center at the University of Minnesota, Twin Cities. He is now a senior research scientist for the Natural Health Products Research Group at the British Columbia Institute of Technology in the Vancouver area.

McKenna received his Master's degree in botany at the University of Hawaii in 1979. He received his Doctorate in Botanical Sciences in 1984 from the University of British Columbia, where he wrote a dissertation entitled Monoamine oxidase inhibitors in Amazonian hallucinogenic plants: ethnobotanical, phytochemical, and pharmacological investigations. His research has included the pharmacology, botany, and chemistry of ayahuasca and oo-koo-hé, the subjects of his master's thesis. He has also conducted extensive fieldwork in the Peruvian, Colombian, and Brazilian Amazon.

See also

Christian Rätsch

Christophe Wiart

External links

Heffter Research Institute, biography and publications

She Who Remembers Audio Archives of Terrence and Dennis McKenna interviews (MP3s).

Biography page for the Center for Spirituality and Healing

2009 - Cognition Factor (2009)

Category:1950 births Category:Living people Category:Psychedelic researchers Category:Psychedelic drug advocates