glycosides introduction

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chemistry of natural products


  • 1. 1 GLYCOSIDES(ANTHRAQUINONES) Presented by; M Pharm (Pharmaceutical Chemistry) students Gunturu. Aparna Akshintala. Sree Gayatri Thota. Madhu latha Kamre. Sunil Daram. Sekhar University College Of Pharmaceutical Sciences Department Of Pharmaceutical Chemistry Acharya Nagarjuna University Guntur

2. 2 Glycosides Definition: Organic natural compounds present in a lot of plants and some animals, these compounds upon hydrolysis give one or more sugars (glycone) - form and non sugar (aglycone) or called genin. 3. 3 Glycosides More important in medicine than a lot of drugs. Occur in higher plant tissues in very small amounts Also fungal and bacterial cells (exuded in medium) and animals Formed by a biochemical reaction that makes a water insoluble compound more polar than a water soluble molecule Hence can be removed from an organic system Man forms them in the liver as part of the process of detoxification and they are excreted via urine Mammalian glycosides are simple compounds whereas plant glycosides are much larger and chemically more complex 4. 4 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. 5. 5 Separation between glycosides parts: Glycosides glycone +aglycone +HCl G + A +salt+H2O (H2O+G) + A (H2O+G) + (chloroform+A) We can separate them by using separating funnel. The best solvent to extract aglycone is Ethyl acetate because: A. Immiscible in water. B. Always presents in the upper layer. Neutralization by Using alkaline Filtration chloroform Hydrolysis +HCLdil 6. 6 Note: Alcohol and acetone are water miscible compounds , so we can't use them as organic solvents for aglycone separation. 7. 7 Physico-chemical properties of glycosides(general) Colorless, solid, amorphous, nonvolatile (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). 8. 8 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. 9. 9 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). 10. 10 Some glycosides have antibacterial activity, so they protect the plants from bacteria and diseases. Bitter almond Amygdalin bacteria HCNhydrolysis kill Eomlsin enzyme 11. 11 Classification of glycosides 12. 12 Classifications of glycosides according to their therapeutic effects CHF(Congestive Heart Failure)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. Convolloside:Convallaria majalis Lily of the Valley. 13. 13 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). 14. 14 Local irritant group: a. Sinigrin (Black mustered seeds-Brassica nigra) b. Sinalbin (White mustered seeds-Brasica alba) Analgesics and antipyretics: Salicin Salisylic 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 15. 15 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. 16. 16 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 a oxygen atom of aglycone . S-glycosides : In these glycosides the sugar attached to a Sulfur atom of aglycone ,for example sinigrin. N-glycosides : In these glycosides the sugar linked with Nitrogen atom of (-NH2,-NH-)amino group of aglycone ,for example nucleosides DNA,RNA. C-glycosides : In these glycosides the sugar linked (condensed) directly to Carbon atom of aglycone ,for example aloin. 17. Most of glycoside may be named according to the plant from which they isolated for example: 1. Salicin from salix 2. Cascarosides from cascara 3. Aloin from Aloe vera 4. Sennosides from senna 5. Frangulin from frangula 6. Glycyrrhizin from glycyrrhiza GENERAL EXTRACTION PROCESS OF GLYCOSIDES; Always glycosides founded in the plant with the enzymes which hydrolyzed them. We must damage these enzymes first to extract these glycoside by the following steps: STEP 1. Drying the plants fresh in special oven at 1000c for 30 minutes. STEP 2. Boiling them with organic solvents for 20 minutes STEP 3. Boiling them with acetone 5 minutes 17 18. 18 METHYL GLYCOSIDES Methylglucoside is a monosaccharide derived from glucose. It can be prepared in the laboratory by the acid-catalyzed reaction of glucose with methanol. 19. 19 USES: chemical intermediate in the production of a variety of products including Emollients. Emulsifiers. humectants. moisturizers. thickening agents. plasticizers. Surfactants. varnishes and resins. 20. 20 Preparation of methyl glycoside STEP 1: Methyl glucoside is prepared by the acid-catalyzed reaction of glucose and methanol . In the reaction glucose, methanol and acid catalyst, anhydrous hydratable CaSO4 are required . In the .preparation of methyl glycoside CaSO4 :glucose weight ratio of at least 1:1, maintaining the reaction mixture within the temperature range of about 50 C and 200 C until formation of methyl glucoside ceases. 21. 21 cooling the reaction mixture, neutralizing the acid catalyst with a base capable of forming a salt of neutralization which is insoluble in the reaction mixture . acid catalystC6 H12 O6 +CH3 OHmethylglucoside+H2 O (I) 22. 22 2. Process according to step 1, wherein the CaSO4 is incorporated in the reaction mixture in an amount sufficient to provide a CaSO4:glucose weight ratio from about 1:1 to about 3:1 3. Process according to step 1, wherein the CaSO4 :glucose weight ratio is from about 1:1 to about 2:1 4. Process according to claim 1, wherein the acid catalyst is H2 SO4. 5. Process according to step 4, wherein the base is selected from the group consisting essentially of Ca(OH)2, Mg(OH)2, Ba(OH)2, Sr(OH)2and mixtures there of. 6. Process according to step 1, wherein the reaction is carried out in a closed vessel within the temperature range of about 100 C and 150 C 23. 23 Anthraquinone Glycosides ( Anthraquinone Anthraquinone derivatives 24. 24 Aloe barbadensis Cassia senna Rhamnus purhsianus - Cascara Rheum palmatum. Chinese Rhubarb 25. 25 Introduction to Anthraquinones Historically: Rhubarb, Senna, Aloes and Cascara were all used as purgative drugs. Monocotyledons: Only Liliaceae. Most commonly C-glycoside: barbaloin. Dicotyledons: Rubiaceae, Leguminosae, Polygonaceae, Rhamnaceae, Ericaceae, Euphorbiaceae, Lythraceae, Saxifragaceae, Scrophulariaceae andVerbenacacea. Also in certain fungi and lichen. 26. 26 Reduced derivatives of anthraquinones Oxanthrones, anthranols and anthrones Compounds formed by the union of 2 anthrone molecules Dianthrones Aglycones: Chrysophanol/Chrysophanic acid Rhubarb and Senna. Rhein Rhubarb and Senna Aloe-emodin Rhubarb and Senna Emodin Rhubarb and Cascara 27. 27 Anthraquinones Chemical Properties Anthraquinone derivatives: orange-red compounds Soluble in hot water/dilute alcohol. Identified via Borntragers test Powdered drug macerated with ether Filter Add ammonia/caustic Shake pink, red or violet colour positive for anthraquinone derivatives If the Anthraquinones are reduced (within the herb) or stable (glycosides) test will be negative 28. 28 Anthraquinone Structure 29. 29 Anthranonls andAnthrones Reduced anthraquinone derivatives. Occur either freely (aglycones) or as glycosides. Isomers. Anthrone: Parent structure (pale yellow, non- soluble in alkali, non-fluorescent) Anthronol: brown-yellow, soluble in alkali, strongly fluorescent Anthronol derivatives (e.g. in Aloe have similar properties fluorescence used for identification) 30. 30 Oxanthrones Found in Cascara bark Intermediate products (between anthraquinones and anthranols) When oxidised oxanthrones it form anthraquinones Oxanthrones are detected by Modified BorntragersTest (oxanthrones oxidised using hydrogen peroxide) oxanthrone 31. Dianthrones Derived from 2 anthrone molecules 2 molecules may/not be identical Dianthrones are form easily due to mild oxidation of anthrones It form important aglycones Cassia Rheum 31 32. 32 33. 33 General structure of glycoside Structure-Activity Relationship 34. 34 Glycosylation is essential for activity. Hydroxylation at C-1 and C-8 is essential for activity. Oxidation level at C-9 and C-10 is important: Highest level of oxidation (anthraquinones) have the lowest activity. Oxanthrones are less active than anthrones. Complete reduction of C-9 and C-10 eli