Cinchona trees have a limited range of natural distribution. It grows wild only in South America – in Peru, Bolivia, Ecuador and Colombia, on the eastern slopes of the Andes, at an altitude of 1600-3200 m above sea level. m. in moist forests among other trees; continuous thickets do not form.
The medicinal properties of a decoction of cinchona bark for malaria were discovered by the Indians. This Indian “red water” in 1638 was cured by the wife of the viceroy of Peru, Ana del Chin-chon (the tree is named Cinchona in her honor). The Queen considered it necessary to acquaint Europe with this “miraculous” remedy, where malaria was also often ill, but there were no cures for it. Soon this tool was appreciated in Europe and the bark began to be sent from Peru in large quantities. Trees were rapaciously cut down and by the middle of the 19th century. the nearness of their complete destruction became obvious. The introduction of the cinchona tree into cultivation was required, but there were no enterprising organizers, and the Peruvian government did not want to lose its profitable monopoly on the sale of cinchona bark and did not provide seed. Nevertheless, the German botanist Hasskarl, with great difficulty, managed to collect seeds and seedlings and transport them to about. Java. For the second time, a large consignment of bkla seeds was stolen from Peru by the English merchant Charles Ledger and also delivered to about. Java.
It took many years of work to master the culture of cinchona trees and increase their alkaloid content through selection. Currently, there are plantations in various places in Southeast Asia, in India, Sri Lanka, Indonesia, Asia Minor, East Africa, on the Reunion Islands, Madagascar and at home in Latin America.
The taxonomy of the genus is not well understood. There are many natural and artificial hybrids in culture. There are up to 40 species in the genus, mainly 5 in culture: C. succirubra Pav., C. calisaya Wedd., C. ledgeriana Moens, C. officinalis L., C. pitayensis Wedd.
C. succirubra Pav. – cinchona red-bark, is an evergreen tree up to 20 m tall with opposite, leathery, shiny, bright green, broadly elliptical leaves. The flowers are tubular, five-membered, light pink on the outside, white inside the corolla lobes, with a pink middle stripe, collected in panicles at the tops of stems and branches. The tree is very decorative and somewhat resembles lilac. The fruit is a dry two-celled capsule; the seeds are small, with a wide feathery fly. Other types of cinchona are smaller in height and differ in leaf shade, flower size, corolla color, and other features. So, in C. ledgeriana Moens, the leaves are dark green with a red median nerve, and the flowers are small, yellowish or pure white.
On plantations in the 6-7th year, after sowing the seeds, grown trees that are too densely standing are uprooted and the entire bark is removed. Thinning is carried out annually, and 25-year-old plantations are traditionally eliminated, but a new site is pre-sown to replace it. The bark (Cortex Chinae) is removed both in straight tubes, which are considered the first grade, and in uneven pieces. The bark is traditionally air-dried. Outside, the cinchona bark is covered with a dark brown cork, often bearing lichens, the inner surface of the bark is smooth, reddish-brown, the fracture is coarsely fibrous, the taste is very bitter, there is no smell.
Cinchona bark contains a mixture of alkaloids. In different types of cinchona trees, 25 various alkaloids were found, but quinine is the main one in action. Quinine was first discovered by the Russian doctor F. Giese in Kharkov in 1818, but his work was not known. In 1820, quinine was rediscovered by the French pharmaceutical scientists Pelletier and Cavantou. The structure of quinine was established in 1907, and the synthesis was carried out in 1944.
Quinine contains a quinuclidine ring, which consists of two fused piperidine rings. Another important alkaloid is cinchonine, which differs from quinine in the absence of a methoxyl group. Both of these alkaloids are also presented in the form of their isomers – quinidine (conquinine) and cinchonidine.
Depending on the type of cinchona, the bark contains different amounts of the main alkaloids (both in total and separately). Thus, the bark of C. vicarita pau., used for the preparation of galenic products, contains at least 6.5% of the total alkaloids with a low content of quinine. The largest number of alkaloids accumulates in the bark of C. edgeriana Moens (12-20%), with quinine accounting for most of the total (up to 13%); for this reason it is used to obtain quinine. For the same purpose, the bark is also used, in which a relatively small amount of alkaloids (7-8%) consists of 90% quinine.
The remaining alkaloids are found in small amounts and not in all forms. In addition to alkaloids, in cinchona bark used for galenic products (extracts, etc.), tannins of the pyrocatechin group, quinovine glycoside and resins are important. Galenic products are used as appetite stimulants and gastric agents.
Cinchona bark alkaloids are isolated from the bark by extraction with an organic extractant in an alkaline medium. The extract containing the sum of base alkaloids is treated with sulfuric acid; crude quinine sulfate precipitates. Further, a mixture of crystallizing alkaloids cinchonidine, quinidine and cinchonine is isolated from the mother liquor. After their separation, a brown resinous mass remains – quinoidine, containing a mixture of various amorphous alkaloids, among which diconquinine prevails.
Other easily soluble salts are prepared from raw quinine sulfate – quinine hydrochloride, quinine dihydrochloride, quinine sulfate and quinidine. Quinine salts are an effective antimalarial agent. In obstetric practice, quinine salts (usually hydrochloride) are prescribed to induce and enhance labor activity. Quinidine is used as an antiarrhythmic agent for the treatment of extrasystole, persistent atrial fibrillation, tachycardia.
The plant contains quinoline alkaloids.
PLANTS CONTAINING ALKALOIDS
Alkaloids are called natural nitrogen-containing compounds of the main character, formed in plants. Groups of proteinogenic amines (for example, tyramine) and betaines (stakhidrin, trigonelline, etc.) adjoin the alkaloids, which are considered as transitional compounds from the simplest nitrogen-containing compounds (methylamine, trimethylamines, etc.) to the alkaloids themselves.
Of natural pharmacologically active substances, alkaloids are the main group from which modern medicine draws the largest number of highly effective drugs.
According to world literature, by the end of the past decade, the number of alkaloids isolated from the higher plants of the Earth’s flora exceeded 5000. According to modern concepts, alkaloid-bearing plants make up 10% of the entire world flora. The families Equisetaceae, Lycopodiaceae, Ephedraceae, Liliaceae, Amaryllidaceae, Dioscoreaceae, Chenopodiaceae, Nymphaeaceae, Ranunculaceae, Berberidaceae, Menispermaceae, Papaveraceae, Fabaceae, Rutaceae, Cactaceae, Punicaceae contain the largest number of alkaloid-bearing genera and species. Loganiaceae, Apocynaceae, Borraginaceae, Solanaceae, Rubiaceae.
Usually plants that are phylogenetically close contain alkaloids that are very similar in structure, thus forming a natural group of genera. For example, plants of the genera Atropa, Datura, Hyoscyamys, Scopolia, Physochlaina, Duboisia. Mandragora (all from the same Solananeae family) contain a well-defined group of tropane alkaloids. This far-reaching pattern, however, has exceptions that have not yet been explained. So, for example, caffeine is found in plants that are not systematically related to each other: tea (Theaceae), coffee (Rubiaceae), cocoa (Sterculiaceae), mate (Aquifoliaceae), guarana (Sapindaceae), erodium (Geraniaceae). Along with this, there are cases when their 2 very close systematically species, one is rich in alkaloids, and the other either does not contain them at all, or contains alkaloids of a different structure.
Alkaloids can be found throughout the plant, or they can be formed and accumulated only in one or more specific organs. The plant traditionally contains not one, but several alkaloids. In individual plants, there may be 20 or more of them (cinchona, hypnotic poppy, etc.), and they may be similar in structure or belong to different chemical groups. In the sum of alkaloids, 1–3 traditionally predominate quantitatively (the main alkaloids). In plants, alkaloids are dissolved in the cell sap of the main parenchyma, phloem, and other tissues in the form of salts, mainly organic acids (malic, succinic, citric, oxalic, fumaric, quinic, etc.); of mineral acids, phosphoric acid is more often involved.
The quantitative content of alkaloids is, in principle, a species characteristic, and it varies over a very wide range. For example, in black henbane they are only 0.05-0.1%, and up to 15% accumulate in the cinchona bark. In the process of ontogenetic development of plants, their alkaloid content undergoes quantitative and sometimes qualitative changes, and each species has its own regularities.
The content of alkaloids in plants is influenced by their geographical location and various factors (air and soil temperature, precipitation, duration and intensity of sunlight, shading, height above sea level, etc.), as well as human impact in the case of transferring the plant to cultivation or its acclimatization. The largest number of alkaloid-bearing species, moreover, with a high content of alkaloids, is common in subtropical and tropical states with a humid climate. Alkaloids of different structure are confined to certain latitudes, and in connection with this, their pharmacological activity changes.
There is no consensus on the biological role and causes of the formation of alkaloids in plants. The main hypotheses proposed at different times interpret alkaloids as: 1) waste products of the vital activity of a plant organism; 2) spare substances; 3) protective substances; 4) active substances necessary for biosynthesis. The latter hypothesis is currently considered by most scientists to be the most general one, which, however, does not exclude other biological functions of alkaloids.
The exceptional diversity in the structure of alkaloid molecules does not allow us to imagine a single way of their formation in plants. Their biosynthesis proceeds according to specific schemes with the most complex chemical transformations (ring opening and closing, oxidation, deamination, ring condensation, etc.) through many intermediate products. Some alkaloids begin biogenesis from amino acids, others from acetic acid (in other words, from carbohydrates).
The modern classification of alkaloids is based on the nature of the heterocycles included in their molecules, with the release into a separate group of alkaloids with an aliphatic structure and with nitrogen in the side chain.
1. Alkaloids with an aliphatic structure or with nitrogen in the side chain;
2. Pyrrolizidine alkaloids.
3. Piperidine and pyridine alkaloids.
4. Alkaloids with condensed and pyrrolidone and piperidine rings.
5. Quinoline alkaloids.
6. Quinazoline alkaloids.
7. Isoquinoline alkaloids.
8. Indole alkaloids.
9. Alkaloid of the imidazole group.
10. Purine alkaloids.
11. Diterpene alkaloids.
12. Steroid alkaloids (glycoalkaloids).
13. Alkaloids of unknown structure.
In conclusion of this brief review, it should be pointed out that most alkaloids are highly active substances with selective pharmacological action. The selectivity of the action of alkaloids determines their widespread use for medicinal purposes. The main forms are extraction products (tinctures, extracts, novogalenic preparations, etc.) and pure alkaloids isolated from plants, converted into soluble salts of certain inorganic and organic acids.