CHAPTER VI
GLUCOSIDES
Strictly speaking, the term _glucoside_ should be applied only to such compounds as contain glucose as the characteristic basic group. But in common usage, it refers to any compound which, when hydrolyzed, yields a sugar as one of the products of the hydrolysis. In all the natural glucosides which occur in plant tissues, the other organic constituent, which is represented by the R in the formula for glucosides (R·C_{6}H_{11}O_{5}, or R·(CHOH)_{5}CHO) is some aromatic group, or closed-ring benzene derivative.[3] The different organic constituents of glucosides are of a great variety of types, such as phenols, alcohols, aldehydes, acids, oxyflavone derivatives, mustard oils, etc. It is noteworthy, however, that no nitrogenous groups of the protein type have been found combined with sugars in glucosides.
Some glucosides contain more than one saccharide group, possibly as di- or trisaccharides. Under proper conditions of hydrolysis, one or more of the saccharide groups can be removed from such compounds, resulting in glucosides of simpler structure.
Most of the common glucosides are derived from _d_-glucose. Some are known, however, which are derivatives of galactose or rhamnose; while in some cases the exact nature of the sugar which is present has not yet been determined.
FOOTNOTES:
[3]
HC // \ HC CH The structural formula for benzene, C_{6}H_{6}, | ¦ is one which it is HC CH \\ / CH
difficult and inconvenient to reproduce in type. On that account, it is
/\ customary to indicate this formula by a plane hexagon, thus | |. \/
It is understood, in all such cases, that the figure represents six carbon atoms arranged in a closed ring, with alternate double and single bonds, and with a hydrogen atom attached to each carbon. The printing of some other group as OH, CH_{3}, adjacent to an angle of the hexagon means that this group replaces the H atom in the compound which is being illustrated.
HYDROLYSIS OF THE NATURAL GLUCOSIDES
All natural glucosides are hydrolyzed into a sugar and another organic residue by boiling with mineral acids; although they vary widely in the ease with which this hydrolysis is brought about.
In most cases, the glucoside is easily hydrolyzed by an enzyme which occurs in the same plant tissue, but in different cells than those which contain the glucoside. Injury to the tissues, germination processes, and perhaps other physiological activities of the cells, result in bringing the enzyme in contact with the glucoside and the hydrolysis of the latter takes place. A large number of such enzymes have been found in plants, many of which hydrolyze only a single glucoside. However, two enzymes, namely, the emulsin of almond kernels, and _myrosin_ of black mustard seeds, each hydrolyze a considerable number of glucosides. In general, _emulsin_ will aid in the hydrolysis of any glucoside which is a derivative of [beta]-glucose, and myrosin will help to split up any sulfur-containing glucoside. Glucosides which are derivatives of rhamnose require a special enzyme, known as _rhamnase_, for their hydrolysis.
The following reactions for the hydrolysis of arbutin and of amygdalin are typical of this action, and will serve to illustrate the general structure of these compounds:
------O------- | | CH_{2}OH·CHOH·CH·CHOH·CHOH·CH·O·C_{6}H_{4}OH + H_{2}O Arbutin = C_{6}H_{12}O_{6} + HOC_{6}H_{4}OH Glucose Hydroquinone
C_{6}H_{5} | (_a_) C_{6}H_{11}O_{5}·O·C_{6}H_{10}O_{4}·O·CH + H_{2}O Amygdalin | CN C_{6}H_{5} | = C_{6}H_{11}O_{5}·O·CH + C_{6}H_{12}O_{6} Mandelo-nitrile | Glucose glucoside CN
C_{6}H_{5} | (_b_) C_{6}H_{11}O_{5}·O·CH+H_{2}O = C_{6}H_{5}·CHOH·CN+C_{6}H_{12}O_{6} Mandelo-nitrile | Mandelo-nitrile Glucose glucoside CN
(_c_) C_{6}H_{5}·CHOH·CN + H_{2}O = C_{6}H_{5}·CHO + HCN Mandelo-nitrile Benzaldehyde Hydrocyanic acid
GENERAL PROPERTIES OF GLUCOSIDES
As a rule, glucosides are easily soluble in water. They are generally extracted from plant tissues by digestion with water or alcohol. In most cases, the enzyme which is present in other cells of the same tissue must be killed by heating the material, in a moist condition, to the temperature of boiling water, before the extraction is begun, as otherwise the glucoside will be hydrolyzed as rapidly as it is extracted from its parent cell. Maceration or otherwise bruising the tissue, after the enzyme has been destroyed, facilitates the extraction. The glucosides, after extraction and purification by recrystallization, are generally colorless, crystalline solids, having a bitter taste and levorotatory optical
## activity. This latter property is remarkable, as most of them are compounds
of the strongly dextrorotatory _d_-glucose.
Many of the natural glucosides have marked therapeutic properties and are largely used as medicines; others are the mother-substances for brilliant dyes; for example, indican, from which indigo is obtained, and the alizarin glucosides.
Several hundred different glucosides have been isolated from plant tissues, and their properties described, and this number is being added to constantly, as the methods of isolation and study are improved. They may be classified into groups, according to the nature of the organic compound other than sugars which they yield when hydrolyzed. The following descriptions of the occurrence, constitution, products of hydrolysis, and special properties of typical members of each of the several different classes of glucosides will serve to illustrate their general relationship to plant growth.
THE PHENOL GLUCOSIDES
=Arbutin=, C_{12}H_{16}O_{7}, is obtained from the leaves of the bear berry (_Arctostaphylos uva-ursi_), a small evergreen shrub. When hydrolyzed by mineral acids or emulsin, it yields glucose and hydroquinone.
C_{12}H_{16}O_{7}+H_{2}O = C_{6}H_{12}O_{6}+C_{6}H_{4}(OH)_{2}.
Hydroquinone has strongly antiseptic properties. Arbutin is both an antiseptic and a diuretic, and is used in medicine.
=Phloridzin=, C_{21}H_{24}O_{10}, is found in the bark of apple, pear, cherry, plum, and similar trees. Mineral acids (but not emulsin) hydrolyze it to glucose and _phloretin_ (C_{15}H_{14}O_{5}), according to the equation
CH_{3} C_{21}H_{24}O_{10} + H_{2}O = C_{6}H_{12}O_{6} + | (OH)_{3}C_{6}H_{2}·CO·CH·C_{6}H_{4}OH.
It is used in medicine as a remedy for malaria, having marked anti-periodic properties.
=Glycyphyllin=, C_{21}H_{24}O_{9}, found in leaves of Smilax, yields rhamnose and phloretin, when hydrolyzed.
=Iridin=, C_{24}H_{26}O_{13} (glucose and irigenin), found in rootstocks of Iris, is used in medicine as a cathartic and diuretic.
=Baptisin=, C_{26}H_{32}O_{14}·9H_{2}O (two rhamnose and baptigenin), found in roots of wild indigo (_Baptisia_), has strong purgative properties.
=Hesperidin=, C_{50}H_{60}O_{27} (one rhamnose+two glucose+hesperitin), is found in the pulp of lemons and oranges.
The characteristic phenol group which is present in these glucosides has the following structural formula, in each case, the X indicating the H atom which is replaced by the sugar molecule to form the glucoside:
Phloretin
/\ /\ / \----C----CH------/ \ | | ¦ | | |OX HO| |OH O CH_{3} | |OH \ / \ / \/ \/
Irigenin
O / \ -CH_{2}-C-O--/\ /\ \ / \O·CH_{3} / \ O-| | | | | |OX CH_{3}O-| | \ / \ / \/ O | CH_{3}
Hesperitin
/\ /\ / \ / \ HO| |-CH=CH-C-| |OX CH_{3}O| | ¦ | | \ / O \ / \/ \/
THE ALCOHOL GLUCOSIDES
=Salicin=, C_{13}H_{18}O_{7} (glucose+saligenin, or _o_-oxy benzyl alcohol) is found in the bark, leaves, and flowers of most species of willow, the proportion present depending upon the season of the year, and the sex of the tree. It is used as a remedy against fevers and rheumatism, causing less digestive disturbances than the salicylic acid which is the oxidation product of saligenin and which is sometimes used as a remedy for rheumatism.
=Coniferin=, C_{16}H_{22}O_{8} (glucose and coniferyl alcohol), is found in the bark of fir trees. The coniferyl alcohol obtained from coniferin by hydrolysis can be easily oxidized to _vanillin_, and is, therefore, the source for the artificial flavoring extract used as a substitute for the true extract of the vanilla bean.
=Populin=, C_{20}H_{22}O_{8} (glucose+saligenin+benzoic acid), found in the bark of poplar trees, is used in medicine as an antipyretic. It can be hydrolyzed, by a special enzyme, into salicin and benzoic acid.
The structure of the two typical closed-ring alcohols which are present in these glucosides is indicated by the following formulas;
Coniferyl alcohol Saligenin CH=CH·CH_{2}OH /\ /\ / \ / \ | |CH_{2}OH | | | |OX | |OCH_{3} \ / \ / \/ \/ OX
THE ALDEHYDE GLUCOSIDES
=Salinigrin=, C_{13}H_{16}O_{7} (glucose and _m_-oxy benzaldehyde), is found in the bark of one species of willow (_Salix discolor_). Its isomer, known as _helicin_ (glucose and _o_-oxy benzaldehyde, or salicylic aldehyde), does not occur naturally in any plant, but is easily produced artificially by the gentle oxidation of salicin. Their relationships are shown on the following formulas;
Salicin Helicin Salinigrin
/\ /\ /\ / \ / \ / \ | |CH_{2}OH | |CHO | |CHO | |OX | |OX | | \ / \ / \ / \/ \/ \/ OX
=Amygdalin=, also contains a benzaldehyde group, but there is linked with it a hydrocyanic acid group; hence, this glucoside is usually classed with the cyanophoric glucosides (see page 86).
THE ACID GLUCOSIDES
The most common example of this group is =gaultherin=, C_{14}H_{18}O_{8}, which is found in the bark of the black birch and is a combination of glucose with methyl salicylate. Both the glucoside itself and the methyl salicylate ("oil of wintergreen") which is derived from it are used as remedies for rheumatism.
=Jalapin=, C_{44}H_{56}O_{16} (glucose and jalapinic acid), and =convolvulin=, C_{54}H_{96}O_{27} (glucose+rhodeose+convolvulinic acid), are glucosides of very complex organic acids, found in jalap resin, which are used in medicine as cathartics or purgatives.
THE OXY-CUMARIN GLUCOSIDES
Cumarin itself is widely distributed in plants. No glucoside containing cumarin as such has yet been isolated; but several glucosides of its oxy-derivatives are known. The following are common ones:
=Skimmin=, C_{15}H_{16}O_{8} (glucose and skimmetin), is found in _Skimmia japonica_; =æsculin=, C_{15}H_{16}O_{9} (glucose and æsculetin), is found in the bark of the horse-chestnut, _Æsculus hippocastanum_, and its isomer, =daphnin= (glucose and daphnetin), in several species of _Daphne_; and fraxin, C_{16}H_{18}O_{10} (glucose and fraxetin), is found in the bark of several species of ash.
The structural arrangement of the oxy-cumarin groups which are found in these glucosides is shown in the following formulas. It is not known to which OH group the sugar is attached, in each case.
Skimmetin Æsculetin
CH=CH·CO CH=CH·CO /\ | /\ | / \_O_| / \_O_| | | | | | | HO| | \ / \ / \/ \/ OH OH
Daphnetin Fraxetin
CH=CH·CO CH=CH·CO /\ | /\ | / \_O_| / \_O_| | | HO| | | |OH HO| | \ / \ / \/ \/ OH OCH_{3}
=Scopolin=, C_{22}H_{28}O_{14}, found in _Scopolia japonica_, contains two glucose molecules united to a monomethyl ether of æsculin; while =limettin=, found in certain citrus trees, is the dimethyl ether of æsculin.
THE PIGMENT GLUCOSIDES
Many, if not all, of the red, yellow, violet, and blue pigments of plants either exist as, or are derived from, glucosides. These are of three types: the madder, or alizarin, reds are derivatives of various oxy-anthraquinones; most of the soluble yellow pigments are glucosides derived from flavones or xanthones; and the soluble red, blue, and violet pigments of the cell-sap of plants are mostly anthocyan derivatives. The four basic groups, or nuclei, which are present in these different types of compounds are complex groups consisting essentially of two benzene rings linked together through a third ring in which there are either two oxygen atoms in the ring, or one oxygen in the ring and a second attached to the opposite carbon in the (C=O) arrangement, as shown by the following diagrammatic formulas:
Xanthone Anthraquinone
O O ¦ 1 1 ¦ 1' /\ C /\ /\ C /\ / \ / \ / \ / \ / \ / \ | | | |2 2| | | |2' | | | |3 3| | | |3' \ / \ / \ / \ / \ / \ / \/ O \/ \/ C \/ 4 4 ¦ 4' O
Flavone Anthocyan
1 1 /\ O 5'____4' /\ O 5'____4' / \ / \____/ \ / \ / \____/ \ 2| | | \____/3' 2| | | \____/3' 3| | |5 1' 2' 3| | |6 1' 2' \ / \ / \ / \ / \/ C \/ 5 4 ¦ 4 O
The red dyes which were formerly obtained from madder, the powdered roots of _Rubia tinctoria_, but are now almost wholly artificially synthetized, consist of at least four different glucosides, the organic group of which, in each case, is an hydroxy-derivative of anthraquinone. The most important of these is _ruberythric acid_, composed of two molecules of glucose linked with one of alizarin (1,2, dioxyanthraquinone). _Xanthopurpurin_ contains 1,3, dioxyanthraquinone, which is isomeric with alizarin; and _rubiadin_ is a monomethyl (the CH_{3} being in the 4 position), derivative of this compound. _Purpurin_ is a glucoside of 1,2,4, trioxyanthraquinone.
The soluble yellow pigments are generally glucosides of hydroxy-derivatives of xanthone or flavone, known as oxyxanthones or oxyflavones. The sugars which are united to these nuclei vary greatly, so that there are a great variety of yellow, white, or colorless flavone or xanthone pigment compounds. These compounds are almost universally present in plants. For example, one typical set of examinations of the wood, bark, leaves, and flowers of over 240 different species of tropical plants showed that flavone derivatives were present in every sample which was tested, the pigments being usually located in the powdery coating of the epidermis of the tissues.
The following typical examples will serve to illustrate the composition and properties of the glucosides of this type.
=Quercitrin=, C_{21}H_{20}O_{11}, is found in oak bark, in the leaves of horse-chestnut, and in many other plants, often associated with other pigments. It is a brilliant yellow crystalline powder. Industrially, it ranks next to indigo and alizarin in importance as a natural dye stuff. It is a glucoside of rhamnose with 1,3,3',4', tetraoxyflavonol (i.e., the flavone nucleus with five OH groups replacing the hydrogens in the 1, 3, 5, 3', and 4' positions). =Quercetin=, C_{15}H_{10}O_{7}, which is the tetraoxyflavonol itself, without any sugar in combination with it, is found in the leaves of several species of tropical plants and in the bark of others. =Isoquercitrin=, C_{21}H_{20}O_{12}, is derived from the same flavone, but contains glucose instead of rhamnose, as the sugar constituent of the glucoside.
=Apiin=, C_{26}H_{20}O_{9}, the yellow glucoside found in the leaves of parsley, celery, etc., contains apiose (a pentose sugar of very unusual structure, represented by the formula,
CH_{2}OH \ COH·CHOH·CHO), and apigenin, which is a 1,3,4',trioxyflavone. / CH_{2}OH
=Xanthorhamnin=, C_{34}H_{42}O_{20}, is a very complex glucoside containing two rhamnose and one galactose groups, united with rhamnetin, which is quercitin with the H of the OH in either the 1, or 3, position replaced by a methyl group. There are several similar pigments which differ from xanthorhamnin only in the number or position of the methoxy groups (i.e., the OH groups with a CH_{3} replacing the H), or in the nature of the sugar which is present in the compound. Rhamnetin itself is found in the fruits of certain species of _Rhamnus_, and is used in dyeing cotton.
The structural arrangement of the characteristic groups of these flavone pigments will be dealt with more in detail in the chapter dealing with Pigments (