Glycosides Introduction PDF

Glycosides Glycoside: is an organic compound, usually of plant origin, that is composed of a sugar portion linked to a non-sugar moiety by glycosidic bond. The sugar portion is called glycon, The non-sugar portion is called aglycon or genin; In general there are four basic classes of glycosides:C-...

Glycosides Glycoside: is an organic compound, usually of plant origin, that is composed of a sugar portion linked to a non-sugar moiety by glycosidic bond. The sugar portion is called glycon, The non-sugar portion is called aglycon or genin; In general there are four basic classes of glycosides:C- glycosides, in which the sugar is attached to the aglycone through C-C bond, and the O- glycosides in which the sugar is connected to the aglycone through oxygen –carbon bond,S-glycosides and N-glycosides.  therefore glycosides yield one or more sugars among the products upon enzymatic or acid hydrolysis. The sugar component of glycosides may be mono, di, tri or tetrasaccharides.  Alpha and Beta glycosides Sugars in glycosides exist in isomeric α and β forms so both α and β glycosides are theoretically possible. but the β-form is the one that occur in plants The two diastereoisomers differ in configuration about the anomeric carbon (C-1) can exist α and β. If the hydroxyl group on the anomeric carbon is down in relation to the cyclic structure, it is α anomer while if the hydroxyl group on the anomeric carbon is up in relation to the cyclic structure, it is β anomer.  Chemically the glycosides are acetals in which the hydroxyl group (OH) of the glycone is condensed with the hydroxyl group of aglycone. Sugars exist predominantly as cyclic hemiacetals (R-O-C-OH group), while glycosides are usually mixed acetals (R-O-C-O-R) group.  Inside the body the glycosides will be cleaved to glycone and aglycone parts, the glycone part confers on the molecule solubility properties, thus is important in the absorption and distribution in the body, while the aglycone part is responsible for the pharmacological activity. Physical and chemical properties of glycosides Because of the complexity of the structure of the naturally occurring glycosides, no generalization are possible with regard to their stability. In addition there are differences in their solubility properties.  1. Solubility: Most glycosides are soluble in water or hydroalcoholic solutions and insoluble or less soluble in non-polar organic solvents, because the solubility properties of the sugar residues exert a considerable effect i.e. sugar moiety increases water solubility. The aglycon part is soluble in non-polar (organic) solvents like benzene, ether and chloroform.  2. Stability and hydrolytic cleavage: A. Acids and alkali: Glycosides can be hydrolyzed by heating with a dilute acid where by the glycosidic linkages are cleaved, while glycosides are relatively stable towards alkalis. Glycosides can be hydrolyzed by heating with a dilute acid where by the glycosidic linkages are cleaved. Glycosides can be also hydrolyzed by appropriate enzymes, which are usually found in the same plant, in separate compartments. There is a specific enzyme for each glycosides to exert a hydrolytic action on it.  B. Enzyme hydrolysis: Enzymatic hydrolysis: there is a specific enzyme that exerts a hydrolytic action on it. Glycosides can be hydrolyzed by appropriate enzymes, which are usually found in the same plant, in separate compartments. The same enzyme is capable to hydrolyze different glycosides, but α and β stereo-isomers of the same glycoside are usually not hydrolyzed by the same enzyme. Emulsin is found to hydrolyzed most β-glycoside linkages while maltase and invertase are α-glycosidases, capable of hydrolyzing 3. Shape, color, taste and odor A. Shape: Glycosides are solid, amorphous and non volatile. B. Color: Glycosides are colourless except flavonoids are yellow and anthraquinones are red or orange. C. Taste: Most of glycosides are bitter taste. D. Odor: Glycosides are odorless except saponin (glycyrrhizin) Importance of Glycosides 1. Glycosides play an important role in the life of the plant and are involved in different functions. It serve as: A. As sugar reserves B. As waste products of plant metabolism C. As a mean of detoxification D. To regulate osmosis E. To regulate the supply of substances of importance in metabolism F. Has a role of defense against the invasion to the tissues by microorganism some pointed out that aglycones are antiseptics and hence are bactericidal in nature  2. Many therapeutic agents are derived from glycosides. In fact, the group contributes to almost every therapeutic class. A. Some of our most valuable cardiac glycosides from digitalis, strophanthus, squill and others. B. Laxative drugs, such as senna, aloe, rhubarb, cascara sagrada, and frangula, contain emodin and other anthraquinone glycosides; C. Sinigrin, a glycoside from black mustard, yields allyl isothiocyanate, a powerful local irritant. Classification of glycosides 1- According to the type of glycosidic linkage: α-glycosides (α sugar) β-glycosides (β sugar) 2- according to the chemical group of the aglycon involved in the formation of glycoside linkage. Aglycone- O- Sugar O-glycosides(OH group): eg. Senna and rhubarb Aglycone- C- Sugar C-glycosides (C- group): eg. Cascaroside from cascara Aglycone- S- Sugar S-glycosides (SH- group): eg. sinigrin from black mustard Aglycone-N-Sugar: N-glycosides(NH-group): eg. glycoalkaloid. 3- According to the chemical nature of the aglycon, the glycosides containing drugs can be classified into: Cardioactive group. Anthraquinone group. Saponin group. Cyanophore group. Isothiocyanate group. Flavonol group. Alcohol group. Aldehyde group. Phenol group 4- According to the nature of the simple sugar component of the glycoside: 1- Glucoside (the glycone is glucose). 2- Galactoside (the glycone is galactose). 3- Mannoside (the glycone is mannose). 4- Arabinoside (the glycone is arabinose). Biosynthesis of glycosides The biosynthetic pathways are widely variable depending on the type of aglycone as well as the glycone units. The aglycone and the sugar parts are biosynthesized separately, and then coupled to form a glycoside. The coupling of the two parts occurs via phosphorylation of a sugar to yields a sugar 1- phosphate which reacts with a uridine triphosphate to form a uridine diphosphate sugar (UDP-sugar) and inorganic phosphate. This UDP-sugar reacts with the aglycone to form the glycoside and a free UDP sugar phosphorylation sugar-1-P UTP + sugar-1-P UDP – sugar + Ppi UDP – sugar + aglycone sugar – aglycone + UDP (glycoside) Extraction of glycosides Since glycosides are accompanied by specific hydrolyzing enzymes, these enzymes must be inactivated by putting the plant in boiling water or alcohol. Defatting or purification of the plant material in case of seeds. 1. Defatting or purification of the plant material in case of seeds. 2. Treatment with lead acetate to precipitate tannins and other non glycosidal impurities. 3. Removal of any excess of lead acetate by passing hydrogen sulfide H2S gas through the solution. 4. The extract is filtered and concentrated to get crude glycoside. 5. Purification of the crude glycosides by chromatography or crystallization.