Natural Product Glycosides

Glycosides in NP Definition: Organic natural compounds present in a lot of plants and some animals, these compounds upon hydrolysis give one or more sugars (glycone) β-form and non sugar (aglycone) or called genin.

Solubility: glycosides are water soluble compounds and insoluble in the organic solvents. Glycone part: water soluble, insoluble in the organic solvents. Aglycone part: water insoluble, soluble in the organic solvents. Some glycosides soluble in alcohol.

Separation between glycosides parts: Glycosides glycone +aglycone +HCl G + A +salt+H2O We can separate them by using separatory funnel The best solvent to extract aglycone is Ethyl acetate because: A- immiscible in water. B- always presents in the upper layer. Hydrolysis +HCl dil Filtration Neutralization by Using alkaline chloroform

physico-chemical properties of glycosides(general) Colorless, solid, amorphous, nonvolatile (예외: flavonoid-yellow, anthraquinone-red or orange). Give positive reaction with Molisch's and Fehling's solution test (after hydrolysis). They are water soluble compounds, insoluble in organic solvents Most of them have bitter taste (except: populin, glycyrrhizin, stevioside).

Cont... Odorless except saponin (glycyrrhizin). when a glycosides has a lot of sugars its solubility in water decrease. Glycosides hydrolyzed by using mineral acids and temperature or by using enzymes such as: a- Emolsin Bitter almond seeds. b- Myrosin or Myrosinase black mustard seeds. c- Rhamnase glycosides containing rhamnose as sugar part.

Biosynthesis of glycosides (O-glycosides) Uridylyl transferase Enzyme UTP(Uridine Triphoshate) +sugar-1-phoshate UDP-sugar + ppi(Pyrophosphate inorganic). UDP-sugar +acceptor (aglycone) Acceptor-sugar +UDP Glycosyl transferase Enzyme Glycosyl transferase Enzyme

The function or the role of glycosides in the plant organism Converting toxic materials to non or less toxic. Transfer water insoluble substances by using monosaccharide. Source of energy (sugar reservoir). Storing harmful products such as phenol. Regulation for certain functions(growth). Some have beautiful colours(pollenation process).

Cont… Some glycosides have antibacterial activity, so they protect the plants from bacteria and diseases. bacteria kill Bitter almond hydrolysis HCN Amygdalin Eomlsin enzyme

Classification of glycosides

Classifications of glycosides according to their therapeutic effects CHF and cardiac muscles stimulators such as: a-Digitalis glycosides: digoxin, digitoxin, gitoxin (Fox glove leaves). b- Ouabain: Strophanthus gratus seeds. c- K-strophanthin -Strophanthus kombe seeds. d- Scillaren A,B which isolated from red and white Squill bulbs. e- Convalloside: Convallaria majalis – Lily of the Valley.

Digoxin/Convalloside Digitalis purpurea Convallaria majalis

Cont… Laxative group of glycosides: a- Sennoside A,B,C,D (Senna leaves and fruits). b- Cascaroside A,B (Cascara bark). c- Frangulin and glucofrangulin(Frangula bark). d- Aloin and barbaloin (Aloe vera and Aloe barbadensis juice).

Sennoside/Aloin

Cont… Local irritant group: a-Sinigrin(Black mustard seeds_Brassica nigra) b-Sinalbin(White mustard seeds_Brasica alba) Analgesics and antipyretics: Salicin Salicylic acid - Willow or Salix bark. Keeping elasticity of blood vessels like: Rutin_Rutoside (Bitter orange peels, Lemon peels) Anti-inflammatory group: a- Aloin for 1)acne 2)peptic ulcer b-Glycyrrhizin hydrolysis

Sinigrin, Salicin, Rutin Salix spp.

Classification of glycosides according to glycone part Glucose _ glucoside group like in Sennoside. Rhamnose _ Rhamnoside like in frangullin. Digitoxose _ Digitoxoside like in digoxin. Glucose and Rhammnose _ Glucorhamnoside _ glucofrangulin. Rhamnose and glucose _ Rhamnoglucoside _ Rutin.

Classification of glycosides on the basis of the linkage between glycone and aglycone part O-glycosides : in these glycosides the sugar part is linked with alcoholic or phenolic hydroxyl or carboxyl group. S-glycosides : in these glycosides the sugar attached to a Sulfur atom of aglycone such as in sinigrin. N-glycosides : in these glycosides the sugar linked with Nitrogen atom of (-NH2,-NH-)amino group of aglycone like in nucleosides DNA,RNA C-glycosides : in these glycosides the sugar linked (condensed) directly to Carbon atom of aglycone like in aloin.

O,N,S, and C glucoside

Classification of glycosides according to a glycone part : 1- if a glycone part alcohol -this group called alcoholic group like Salicin 2- if a glycone part aldehyde- this group called aldehydic gr. like glucovanillin. 3- if phenol called phenolic group like arbutin . 4-if cyanone called cyanogenic or cyanophoric or cyanoside like amygdalin. 5-if thio called glycosides or isothiocyanate glycoside like sinigrin or sinalbin (-S=C=N-) (SCN) 6-anthracene -------> anthraquinone glycoside –sennoside-. 7-steroid ------ steroidal glycoside (cardiac) Digoxin 8-flavone ,flavonol, flavanone –flavonoid glycoside 9-triterpenoid –saponin glycoside –glycyrrhizin ,melanthin (nigella seeds) or ginsenoside .

Ginseng roots (Panax roots) Panax quinquefolius ,panax ginseng -contains saponin glycoside – ginsenoside ( panaxoside) Triterpenoid + steroidal nucleus Ginseng root uses : 1- stimulant 2- Tonic 3- anti-stress 4-adaptogenic agent . Drugs : 1- geriatric pharmaton 2- gerimax 3- polyvit

Ginseng Saponins

Anthraquinone group of glycosides They are anthracene derivatives (anthracene = is the main nucleus for anthraquinone compounds. In the plant they biosynthesized from acetyl-CoA and malonyl-CoA. They have cathartic property (laxatives and purgative but some of them have anti-inflammatory activity. With hydrolysis they give aglycone part which is di,tri or tetra hydroxy anthracene derivatives. They hydrolyzed only by acids or by enzymes, but not hydrolyzed by alkalines.

6. They have orange or red color (most of them) 7 6.They have orange or red color (most of them) 7.Soluble in water, insoluble in the organic solvents. 8. They have bitter taste and slightly characteristic odor. 9. Anthraquinone may be free state compounds (free from sugar) or anthraquinone glycoside.

Relationship between anthracene derivatives According to linkage between glycone part and aglycone part anthraquinone glycoside may classified to : 1.C-glycoside … very stable to hydrolysis. 2.O-glycoside … 3-o and c- glycoside.

Alcoholic group of glycosides Such as: Salicin which obtained from Salix bark, Willow bark. Salicin hydrolyzed by: 1.Enzyme emolsin 2.Acid like HCl,HNO3 3.Alkaline solutions like NaOH

The effect of salicylic acid : Analgesic. Anti-pyretic. Anti-coagulant (anticlotting agent). Anti- inflammatory activity (Rheumatism) Wart and corn remover Prevents colon cancer

Aldehydic group of glycoside Such as : Glucovanillin which obtained from : Vanilla beans (fruits) ** Vanillin : volatile oil which used as flavoring agent ** vanillin : 1.phenolic group volatile oils 2.aldehyde group of volatile oils

Isothiocyanate group of glycoside ( sulfur glycoside or thio glycoside ) 1. Group of glycosides which contains sulfur (S-glycoside) 2. Present in many cruciferous plants, on hydrolysis. 3. They produce isothiocynate (SCN) aglycone Such as : 1.sinigrin which founded in Black Mustard seeds 2.sinalbin which founded Brassica alba --- White Mustard seeds.

These plants contain also enzyme myrosin (myrosinase) which hydrolyze these glycosides. Properties of Mustard oil : 1.Irritant for mucous membrane 2.Volatile 3.Pungent 4.Characteristic odor The uses of Mustard seeds : counter irritant rubefacient, condiment, emetic in large doses. Drug :Acne aid soap®- Agis Treatment of Acne .

Sinapine : alkaloids – alkaloidal amine group (protoalkaloid properties of Acrinyl isothiocynate. 1.Less irritant than allyl isothiocynate. 2.Less volatile. 3.Odorless. 4.Pungent. Uses of white mustard seeds Condiment, carminative, counter irritant, emetic

Cyanogenic glycosides Group glycosides which widely distributed between the members of Rosaceae family. They gave with hydrolysis HCN (Hydrocyanic acid) They derived from nitrile of mandelic acid. Cyanosides like : Amygdalin : a. Bitter almond seeds. b. Apricots seeds. c. Plums seeds. d. Peaches seeds

2. Prunasin : present in Wild Cherry bark (( Prunus sertina)) Linmarin : Linseeds The plants contain enzyme emolsin which produce during hydrolysis two enzymes 1. Amygdalase hydro. Amygdalin. 2. Prunase hydro.Prunasin. Prunus persica

Flavonoids Large group of glycosides which widely distributed in the plants kingdom and in all plants parts (leaves, roots, rhizomes, fruits peels) Various colors in flowers( yellow, orange, red, purple.) They are benzo-gama-pyrone derivatives. Their chemical structure based on (C6 C3 C6 ). The general uses of Flavonoids and Flavonoid glycosides. Increase elasticity of blood vessels specially Rutin and hesperidin which known as vitamin (p) Anti inflammatory activity like Taxifolin