Glycosides

GLYCOSIDES, substances which, upon hydrolysis by adding elements of water, split into one or more saccharine substances (glucoses) and simple or complex organic compounds (aglycones). The splitting sometimes occurs already upon heating with water, more often upon heating with diluted acids, alkalis, or under the influence of certain enzymes, so-called glycosidases. In most cases, the saccharine part of glycosides is glucose. From this, these compounds received the general name "glycosides," but in view of the presence in them of other sugars (galactose, rhamnose, etc.), galactosides, rhamnosides, or, when several sugars are present, rhamno-glycosides, rhamno-galactosides, etc., are distinguished. The non-saccharine parts of glycosides, the aglycones, are very diverse substances in composition and chemical character. They may be alcohols, phenols, oxyanthraquinones, coloring matters, mustard oils, aldehydes, prussic acid, etc. According to their chemical character, aglycones of glycosides can also be distributed into groups, but in view of the insufficient study of glycosides, a developed classification of them does not exist, and different authors give various classifications, sometimes even guided by botanical features of plants (families). Glycosides are especially frequently found in plants. Bourquelot considers that glycosides are probably formed in leaves, since they are most frequently found in leaves, while in other organs they may not be present. In some families of plants, glycosides have not yet been found, while in others they have been found and even several (ten or more) glycosides, for example, in the leaves of foxglove, in the rhizome of rhubarb, etc. Glycosides, in view of their wide distribution in plants, probably play an outstanding role in various physiological processes, but opinions of researchers on this matter vary. The quantity of glycosides varies depending on the age of the plants, the place of growth, climate, and other conditions. Glycosides exert, for the most part, a specific action on the human and animal organism and therefore are important medicinal agents. Glycosides are solid, non-volatile, mostly crystalline compounds, less often amorphous, colorless, but can also be colored (more often yellow). In most cases, they dissolve in water and alcohol, usually giving neutral reaction solutions; insoluble in water, they may dissolve in ether, acetic ether, chloroform, and other organic solvents; the taste is most often bitter. Very many are optically active, natural glycosides showing in most cases left-handed rotation. In relation to chemical reagents, glycosides react very differently, which depends on the various properties of the sugars formed upon splitting, and especially on the non-saccharine parts, the aglycones. Glycosides do not reduce Fehling's liquid and ammoniacal silver solution at low temperatures and in general do not give other typical reactions of glucoses and are considered as ether-like compounds of glucose with aglycones. Glucose is assigned a structure without a free aldehyde group, which passes into a dihydroxyl group with the formation of a lactone ring from one hydroxyl: /H CH_aON-CH.ON-CH.ON-CH.ON-CH.ON-CH...-*.-<^H : _1 ON CH.ON-CH.ON-CH-CH.ON-CH.ON in which the carbon becomes asymmetric and, depending on the arrangement of groups, gives two spatial isomers, which in the state of equilibrium are distinguished as alpha- and beta-glucoses (Pictet). g n 2 n -ON -ON 3 NO-CH-CH 4 H 5 N 6 NO-NO- CHON OH alpha-glucose I n -CH-ON CH.ON ^-glucose II n-O-OH n - n -CH-ON CH_bON beta-glycoside III The OH group formed by alpha- and beta-glucoses enters very energetically into reaction; it can pass again into an aldehyde group or easily enters into an ether-like bond with a large number of oxygen and other compounds with the elimination of a molecule of water and the formation of glycosides (III). Heating glucose with methyl alcohol and a small amount of HCl, Fischer obtained alpha- and beta-methyl-glycosides. By this and other methods, many artificial glycosides with a more complex composition were obtained. Artificial glycosides corresponding to both forms of glucose can be alpha- and beta-series, differing in right and left rotation. The glycosidic ether bond is more or less easily split back upon the addition of water into hydroxyl compounds, aglycones and alpha-, beta-glucose: A-O-CH + H.O-»- AOH + H.O-CH. 1\

|\ In relation to hydrolytic enzymes (hydrolases), alpha- and beta-glycosides differ sharply, Fischer showing that enzymes from yeast split only alpha-glycosides, while emulsin, the enzyme from bitter almonds, splits only beta-glycosides. Natural glycosides relate to enzymes in the same way, the majority of plant glycosides belonging to the D-series, rotating to the left and being split by emulsin (Bourquelot). For the synthesis of glycosides, in addition to the above-mentioned action of hydrochloric acid on an alcoholic solution of glucose, two methods are of greatest importance: the first, which proved very successful in the hands of Fischer, is based on the use of aceto-bromo-glucose, which, upon the separation of its halide in an alcoholic-alkaline solution or under the influence of silver carbonate, enters into a glycosidic bond with phenols and other substances, and then by the separation of acetyl groups gives free glycosides. The second method, biochemical, is based on the reversibility of the action of hydrolytic enzymes. In aqueous solutions, they cause the addition of water and the splitting of glycosides. In the absence of water and upon its replacement by alcohol of a certain strength, the opposite reaction occurs: the enzyme acts, separating water, the sugar combining with the alcohol in a glycoside. The method was developed by Bourquelot, emulsin giving rise to beta-glycosides, and enzymes from yeast giving alpha-glycosides. Methods for obtaining natural glycosides vary greatly depending on their properties and solubility. In view of the easy decomposition of glycosides, their obtaining is often associated with significant difficulties; enzymes present in plants along with glycosides sometimes split glycosides already during drying or upon processing of plants, so that glycosides cannot be obtained, or they are obtained not as primary but as secondary glycosides. To eliminate the action of enzymes, parts of plants are quickly heated to 70-80° and poured with water of the same temperature, or parts of plants are placed in boiling alcohol, to which a little chalk is added to bind acids. After cooling, they are filtered, alcohol is distilled off, and from the thick extract, glycosides are obtained by extraction with water, acetic ether, and other solvents, after which they are crystallized. Sometimes it is necessary to purify the extract from tannic and other substances by lead acetate or to precipitate glycosides with tannin. The following reactions are used for the determination of glycosides: glycosides dissolved in water, with a grain of bile, upon layering on strong sulfuric acid, give a blood-red ring. The reaction is conditioned by the presence of sugars. Upon boiling glycosides with diluted mineral acids, splitting of glycosides occurs, the aglycones being separated in the form of a crystalline or amorphous precipitate or in the form of a liquid, sometimes with a peculiar odor. The filtered aqueous solution, however, acquires the ability to reduce Fehling's solution and give glucose reactions. Some of the glycosides are precipitated by tannin, part of them gives color reactions with strong sulfuric acid and other reagents. For testing plants for glycosides, Bourquelot developed a general biochemical method based on the splitting of beta-glycosides by emulsin. A water solution of glycosides or an alcoholic extract of the plant, after splitting of cane and other types of sugar by yeast powder, under the influence of emulsin gives a decrease in left-handed rotation and even a transition to right-handed rotation, since beta-glycosides rotate to the left, while the glucose obtained from them rotates to the right. The presence of glycosides is judged by the change in optical rotation, as well as by the change in the ability to reduce copper, and the quantity is judged by the strength of the change in optical properties. Bourquelot's method, however, is not applicable to glycosides not split by emulsin. Therefore, in recent years Briedel and Charaux proposed to carry out tests under the conditions indicated by Bourquelot and with the aid of rhamno-diastase, the enzyme from the berries of Rhamnus utilis, which splits glycoside-rhamnosides, very widely distributed in plants and giving rhamnose upon splitting. General methods for the quantitative determination of glycosides are still little developed and are mostly little used. Glycosides in pure form have not yet received wide application. So far, therapeutically important glycosides continue to be widely used in the composition of parts of plants containing them or in the form of preparations prepared from plants. This creates, in view of the variability of glycosides and the difficulty of their chemical control in plants, the necessity of determining for parts of plants their pharmacodynamic value (valorization) by experiments on animals. Such methods have been adopted for digitalis, adonis, and strophanthus. Discovery of glycosides in judicial cases. Glycosides easily decompose in the living organism, in the corpse, and during chemical treatment; therefore, they can be found in parts of the corpse only in exceptionally rare cases upon extraction with alcohol; chemical reactions described for glycosides are little reliable, and therefore it is necessary to resort to biological testing.