Hydrolysis of Glycosides PDF

# Hydrolysis of Glycosides ## Hydrolysis of glycosides (cont.) The stability towards hydrolysis with acid is related to the nature of the sugar: - Glycosides containing 2-desoxysugar are easily hydrolyzed with acid (e.g. cardiac glycosides) are cleaved by weak acids even at room temperature. - Gly...

# Hydrolysis of Glycosides ## Hydrolysis of glycosides (cont.) The stability towards hydrolysis with acid is related to the nature of the sugar: - Glycosides containing 2-desoxysugar are easily hydrolyzed with acid (e.g. cardiac glycosides) are cleaved by weak acids even at room temperature. - Glycosides containing normal sugar are quite resistant to hydrolysis with acid and need strong acids with heating. - It must be noted that C-glycosides require an oxidizing agent for hydrolysis, e.g. Ferric chloride (FeCl3), hydrogen peroxide (H2O2) ... etc. ## Hydrolysis of glycosides (cont.) ### Hydrolysis by alkali: - Alkalies do not affect the glycosidic linkage. - Cause breakage either in the aglycone or in the sugar portion. - Lactone ring of the cardiac glycosides is opened by strong alkali. - The acetyl group attached by ester linkage to one of the sugar units in glycoside may be removed under controlled conditions of mild alkaline hydrolysis. ## Hydrolysis of glycosides (cont.) ### Hydrolysis by Enzymes: - According to the configuration at C-1 of the sugar, glycosides are divided into two main groups, each of which is affected with the corresponding enzyme-group: - Glycosidase affects the α- glycosidic linkage, e.g., Rhamnase for α-rhamnoside. - β- Glycosidase affects the β- glycosidic linkage, e.g. amygdalase, for amygdalin. - Myrosin hydrolyses all sulfur containing glycosides. ## Classification of Glycosides (cont.) ### The nature of glycoside: They are classified into two main groups according to nature. - **Primary glycosides:** - They are the unchanged from which occur naturally in the fresh plant and they are not product of hydrolysis, e.g., Purpurea glycoside A. - **Secondary glycosides:** - They are glycosides which result from the hydrolysis of other glycoside by enzymatic activity with splitting of one or more sugar unit, e.g., Digitoxin. ## Classification of Glycosides (cont.) ### General equation: Primary glycoside, Enzyme -> Secondary glycoside + Terminal Sugar ## CLASSIFICATION ### Chemical Classification According to the nature of aglycone, glycosides. | Chemical nature of the aglycone | Holosides | A specific group in the molecule | Cyanogenic glycosides | Thioglycosides | Aldehydes | Others | |---|---|---|---|---|---|---| | Phenols | | | | | | | | Lactones | | | | | | | | Steroids | | | | | | | | Saponin | | | | | | | | Simple | | | | | | | | Anthraquinones | | | | | | | | Alcohol | | | | | | | | Flavonoid | | | | | | | ## Hydrolysis of glycosides ### Hydrolysis by Acid: - The glycosides are undergo hydrolysis in acid medium but relatively stable in alkaline medium. ## Classification of Glycosides ### According to the configuration of the glycosidic linkage: **1-β-glycosides:** - Here the sugar involved has the β configuration at the hemiacetal carbon. - The majority of plant glycosides isolated are β-glycoside: **2-α-glycosides:** - Here the sugar involved has the α configuration at the hemiacetal carbon; the sugar is usually of the L-series, e.g., L-rhamnose. - There are only few medicinal α-glycosides known, especially the rhamnosides. ## Classification of Glycosides (cont.) ### According to the nature of aglycone, glycosides can be classified into: - **Holosides:** - They are glycosides in which the aglycone is also a sugar, e.g., maltose, lactose and all oligo- and polysaccharides. - **Heterosides:** - They are glycosides in which the aglycone is a non-sugar, e.g., rutin, digitoxin, sinigrin, barbaloin ... etc. ## Classification of Glycosides (cont.) ### Chemical nature of the aglycone into: - Phenol : Arbutin. - Alcohol : Salicin. - Lactone : Daphnin. - Flavone: Rutin. - Anthraquinone : Gluco-aloe-emodin - Aldehyde : Gluco-vanillin. - Cyanophore : Amygdalin. - Thiocyanate : Sinigrin. - Steroid : Digitoxin. - Saponin : Diosgenin ## Classification of Glycosides (cont.) ### A specific group in the molecule: Examples are: - **Cyano-group (CN):** Cyanogenetic glycosides (Amygdalin)- 60% - **Sulphur (S):** Thioglycoside (Sinigrin). ## Glycosides Generally, glycosides are non-reducing substances which on hydrolysis by acids or enzymes yield: - One or more reducing sugar which is known as glycone. - A non-sugar part or parts, which is/are known as aglycone. - They are used in medicine as medicinal agents, and they have possible use as potential source of new drugs. ## Glycosides - Examples are: Cardiac stimulant as digitoxin, laxative as sennoside, local irritant as sinigrin and analgesic as salicin. - They have also important role in the life of the plants themselves; e.g., as regulatory agent, as protective agent ... etc. ## Chemistry Glycosides are considered as acetals or sugar ethers. The -OH gp of the anom.carbon (C-1) of the sug. is replaced by moiety possessing nucleophilic atom such as: O, S, N or C (carbanion) to give the O-, S-, N- or C-glycosides. ## Classification of Glycosides ### Glycosidic linkages **1-O-glycosides:** - The usual and the common linkage between the sugar and the aglycone is an oxygen linkage, connecting the reducing group of sugar and the alcoholic or phenolic hydroxyl-group of the aglycone, e.g., Salicin. **2-S-glycosides:** - The sugar is linked to the thiol (sulfhydryl) group of the aglycone, e.g., sinigrin. **3-N-glycosides:** - The sugar is linked to the amino-group of the aglycone, e.g., Adenosine **4-C-glycosides:** - The sugar is linked to the aglycone by a carbon-carbon bond, e.g., Barbaloin. ## Glycosides linkages (cont.) ### Glycosides linkages The usual and the common linkage between the sugar and the aglycone is an oxygen linkage, connecting the reducing group of sugar and the alcoholic or phenolic hydroxyl-group of the aglycone, e.g., Salicin. - The sugar is linked to the thiol (sulfhydryl) group of the aglycone, e.g., sinigrin. - The sugar is linked to the amino-group of the aglycone, e.g., Adenosine. - The sugar is linked to the aglycone by a carbon-carbon bond, e.g., Barbaloin.