Glycosides Lecture Notes PDF

Glycosides Definition: Compounds that yield one or more sugars upon hydrolysis are known as glycosides. A glycoside is composed of two moieties: 1-Sugar portion (glycone) 2-Non-sugar portion (aglycone or genin). For example, the hydrolysis of Salicin produces a glucose unit and salicyl alcohol. ...

Glycosides Definition: Compounds that yield one or more sugars upon hydrolysis are known as glycosides. A glycoside is composed of two moieties: 1-Sugar portion (glycone) 2-Non-sugar portion (aglycone or genin). For example, the hydrolysis of Salicin produces a glucose unit and salicyl alcohol.  Glycosides of many different aglycones are extensively found in the plant kingdom. Many of these glycosides are formed from phenols, polyphenols, steroidal and terpenoidal alcohols through glycosidic attachment to sugars. By virtue of the aglycone and/or sugar, glycosides are extremely important pharmaceutically and medicinally. For example, digitoxin is a cardiac glycoside found in the foxglove plant (Digitalis purpurea). Sugars: Among the sugars found in natural glycosides: D-glucose is the most prevalent one, but L- rhamnose, D- and L-fructose and L- arabinose also occur quite frequently. Of the pentoses, L-arabinose is more common than D- xylose and the sugars often occur as oligosaccharides. The sugar moiety of a glycoside can be joined to the aglycone in various ways, the most common being via an oxygen atom (O-glycoside). However, this bridging atom can also be a carbon (C-glycoside), a nitrogen (N-glycoside) or a sulphur atom (S-glycoside). Classification: 1-Based on sugar component: Glycosides that contain glucose are called glucoside. Similarly, when the sugars are fructose or galactose, the glycosides are called fructoside or galactoside, respectively. 2-Based on aglycone: Glycosides can be classified on the basis of the structural types of aglycone present in the glycoside. For example, in anthraquinone, flavonoid, iridoid, lignan or steroid glycosides, the aglycones are anthraquinone, flavonoid, iridoid, lignan or steroid, respectively. 3-Based on properties or functions: Glycosides that have ‘soaplike’ properties are called saponins. Similarly, glycosides that liberate hydrocyanic acid (HCN) on hydrolysis are known as cyanogenic glycosides, and glycosides that have an effect on heart muscle are called cardiac glycosides. 1-Cyanogenic glycosides: Amygdalin, prunasin and a number of other related glycosides belong to this class of glycosides, which liberate hydrocyanic acid upon hydrolysis. Biosynthetically, the aglycones of cyanogenic glycosides are derived from L- amino acids e.g. amygdalin from L-phenylalanine. linamarin from L-valine. d-hurrin from L-tyrosine.  Cyanogenic glycosides, particularly amygdalin and prunasin, are found in the kernels of apricots, bitter almonds, cherries, plums and peaches.  The following are a few other sources of cyanogenic glycosides. Pharmaceutical uses and toxicity: The extracts of plants that contain cyanogenic glycosides are used as flavouring agents in many pharmaceutical preparations. Amygdalin has been used in the treatment of cancer (HCN liberated in stomach kills malignant cells), and also as a cough suppressant in various preparations. Excessive ingestion of cyanogenic glycosides can be fatal. Some foodstuffs containing cyanogenic glycosides can cause poisoning (severe gastric irritations and damage) if not properly handled. Test for hydrocyanic acid (HCN): The liberation of hydrocyanic acid due to complete hydrolysis of cyanogenic glycosides can be determined by a simple colour test using sodium picrate paper (yellow), which turns red (sodium isopurpurate) in contact with HCN. 2-Anthracene/anthraquinone glycosides:  The aglycones of anthracene glycosides belong to structural category of anthracene derivatives.  Most of them possess an anthraquinone skeleton, and are called anthraquinone glycosides. The most common sugars present in these glycosides are glucose and rhamnose.  Anthraquinone glycosides are coloured substances, and are the active components in a number of crude drugs, especially with laxative and purgative properties. Anthraquinone aglycone increases peristaltic action of large intestine. A number of ‘over the counter’ laxative preparations contain anthraquinone glycosides. The use of anthraquinone drugs, however, should be restricted to short term treatment of constipation only, as frequent or long term use may cause intestinal tumours.  Anthraquinones are found extensively in various plant species, especially from the families Liliaceae, Polygonaceae, Rhamnaceae, Rubiaceae and Fabaceae.  They are also biosynthesized in micro- organisms, e.g. Penicillium and Aspergillus species. The following structural variations within anthraquinone aglycones are most common in nature.  Dimeric anthraquinone and their derivatives are also present as aglycones in anthraquinone glycoside found in the plant kingdom. 1-Sennosides: The most important anthraquinone glycosides are sennosides, found in the senna leaves and fruits (Cassia senna or Cassia angustifolia). These are, in fact, dimeric anthraquinone glycosides. However, monomeric anthraquinone glycosides are also present in this plant. 2-Cascarosides: Cascara bark (Rhamnus purshianus) contains various anthraquinone O- glycosides, but the main components are the C-glycosides, which are known as cascarosides.  Rhubarb (Rheum palmatum) also contains several different O- glycosides and cascarosides. Rhein 8-O-glucoside  Aloe vera mainly produces anthraquinone C-glycosides, e.g. aloin. Test for anthraquinone glycosides: For free anthraquinones, powdered plant material is mixed with organic solvent and filtered, and an aqueous base, e.g. NaOH or NH4OH solution, is added to it. A pink or violet colour in the base layer indicates the presence of anthraquinones in the plant sample. For O-glycosides, the plant samples are boiled with HCl/H2O to hydrolyse the anthraquinone glycosides to respective aglycones, and the then the above method for free anthraquinones is carried out. For C-glycosides, the plant samples are hydrolysed using FeCl3/HCl, and then the above method for free anthraquinones is carried out. 3-Isoprenoid glycosides: The aglycone of this type of glycoside is biosynthetically derived from isoprene units. There are two major classes of isoprenoid glycosides: saponins and cardiac glycosides. A-Saponins: Saponin glycosides possess ‘soaplike’ behaviour in water, i.e. they produce foam. On hydrolysis, an aglycone is produced, which is called sapogenin. There are two types of sapogenin:  Steroidal and triterpenoidal. Usually, the sugar is attached at C-3 in saponins, because in most sapogenins there is a hydroxyl group at C-3.  Steroidal sapogenin The two major types of steroidal sapogenin are diosgenin and hecogenin. Steroidal saponins are used in the commercial production of sex hormones for clinical use. For example, progesterone is derived from diosgenin.  The most abundant starting material for the synthesis of progesterone is diosgenin isolated from Dioscorea species (wild yam) and fenugreek, formerly supplied from Mexico, and now from China. The spiroketal group attached to the D ring of diosgenin can easily be removed.  Other steroidal hormones, e.g. cortisone and hydrocortisone, can be prepared from the starting material hecogenin (gastroprotective), which can be isolated from Sisal leaves found extensively in East Africa.  Triterpenoidal saponins In triterpenoidal saponins, the aglycone is a triterpene. Most aglycones of triterpenoidal saponins are pentacyclic compounds derived from one of the three basic structural classes represented by α-amyrin, b-amyrin and lupeol. However, tetracyclic triterpenoidal aglycones are also found, e.g. ginsenosides.  These glycosides occur abundantly in many plants, e.g. liquorice contains glycyrrhizinic acid derivatives.  Ginseng roots contain ginsenosides Most crude drugs containing triterpenoid saponins are usually used as expectorants. Three major sources of triterpenoidal glycosides along with their uses are summarized below: B-Cardiac glycosides: Glycosides that exert a prominent effect on heart muscle are called cardiac glycosides, e.g. digitoxin from Digitalis purpurea. Their effect is specifically on myocardial contraction and atrioventricular conduction. The aglycones of cardiac glycosides are steroids with a side-chain containing an unsaturated lactone ring, either five membered lactone (called cardenolides) The sugars present in these glycosides are mainly digitoxose, cymarose, digitalose, rhamnose and sarmentose. Digitoxose, cymarose and sarmentose are 2-deoxysugars. Cardiac glycosides are found only in a few plant families, e.g. Liliaceae, Ranunculaceae, Apocynaceae and Scrophulariaceae are the major sources of these glycosides. Among the cardiac glycosides isolated to date, digitoxin and digoxin, isolated from Digitalis purpurea and Digitalis lanata, respectively, are the two most important cardiotonics.  Digitoxin and digoxin are also found in in Strophanthus seeds and squill. Both these cardiac glycosides are cardenolides, and the sugar present is the 2-deoxysugar (digitoxose). Both sugar and aglycone parts are critical for biological activity. The sugar part possibly is responsible for binding the glycoside to heart muscle, and the aglycone moiety has the desired effect on heart muscle once bound. It has been found that the lactone ring is essential for the pharmacological action. The orientation of the 3-OH groups is also important, and for more prominent activity this has to be β  In large doses these glycosides lead to cardiac arrest and can be fatal, but at lower doses these glycosides are used in the treatment of congestive heart failure.  Cardiac glycosides with bufadienolide skeleton, e.g. proscillaridin A, have been found in plants (e.g. squill, Drimia maritima). C-Iridoid and secoiridoid glycosides: The iridoids and secoiridoids form a large group of plant constituents that are found usually, but not invariably, as glycosides.  For example, harpagoside, an active constituent of Harpagophytum procumbens, is an iridoid glycoside. Plant families, e.g. Lamiaceae (especially genera Phlomis, Stachys and Eremostachys), Gentianaceae, Valerianaceae and Oleaceae, are good sources of these glycosides.  In most natural iridoids and secoiridoids, there is an additional oxygenation (hydroxy) at C-1, which is generally involved in the glycoside formation.  It is also extremely common amongst natural iridoids and secoiridoids, to have a double bond between C-3 and C-4, and a carboxylation at C-11. Changes in functionalities at various other carbons in iridoid and secoiridoid skeletons are also found in nature, as shown below. Some examples of plants that produce irirdoid or secoiridoid glycosides, and their medicinal uses, are summarized below. Devil’s claw (Harpagophytum procumbens):  Is native to South Africa, Namibia and Madagascar.  Traditionally used in the treatment of osteoarthritis, rheumatoid arthritis, indigestion and low back pain.  This plant contains 0.5–3 percent iridoid glycosides. Harpagoside, harpagide and procumbine being the major active iridoid glycosides present. The toxicity of H. procumbens is considered extremely low. To date, there have been no reported side-effects following its use. However, this plant is said to have oxytocic properties and should be avoided in pregnancy. In addition, due to its reflex effect on the digestive system, it should be avoided in patients with gastric or duodenal ulcers Picrorhiza (Picrorhiza kurroa): Is a small perennial herb that grows in hilly parts of India, particularly in the Himalayas. The bitter rhizomes of this plant have been used for thousands of years in Ayurvedic traditional medicine to treat indigestion, dyspepsia, constipation, liver dysfunction, bronchial problems and fever. It is, in combination with various metals, useful in the treatment of acute viral hepatitis.  The active constituents of picrorhiza are a group of iridoid glycosides known as picrosides I–IV and kutkoside.  Oleuropein, a secoiridoid glycoside Fraxinus excelsior (ash tree), Olea europaea (olive tree) and Ligustrum obtusifolium from the family Oleaceae are the major sources of oleuropein.  This compound has hypotensive, antioxidant, antiviral and antimicrobial properties. There is no known toxicity or contraindications for this compound