glycosides
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Glycosides Definition:Glycosides are (usually) non-reducing compounds, on hydrolysis by reagents or enzymes yield one or more reducing sugars among the products of hydrolysis. 1- Alcoholic or phenolic (aglycone): e.g., O-Glycoside 2- Sulphur containing compounds: e.g., S-Glycoside 3- Nitrogen containing compounds: e.g., N-Glycoside 4- C-Glycoside
ALPHA AND BETA GLYCOSIDESSugars exist in isomeric α and β forms. Both α and β Glycosides are theoretically possible. All natural glycosides are of the β Type. Some α linkage exists in sucrose, glycogen andstarch glycoside K-strophanthoside(strophanthidin-linke to strophanthotriose (Cymarose + β-glucose + α- glucose). CLASSIFICATION AND NOMENCLATURE:According to the type of glycosidic linkage: α- glycoside (α-sugar) and β-glycosides (β-sugar). According to the chemical group of the aglycone involved into the acetal union:O-glycoside (OH group) S-glycoside (SH group).N-glycoside (NH group).C-glycoside (C group). According to the nature of the simple sugarcomponent of the glycoside:Glucosides (the glycone is glucose).Galacosides (the glycone is galacose).Mannosides (the glycone is mannose).Arabinosides (the glycone is arabinose). According to the number of the monosaccharides in the sugar moiety:Monoside (one monosaccharide) e.g., salicin.Biosides (two monosaccharide) e.g., gentobioside.Triosides (three monosaccharide) e.g., strophanthotriose.
According to the physiological or pharmacological activity ‘therapeutic classification)Laxative glsycosides.Cardiotonic glycosides. according to the correlation to the parent natural glycosideprimary glycosides e.g., amygdalin, purpurea glycoside A,Secondary glycosides e.g., prunasin, digitoxin. According to the plant families. According to the chemical nature of the aglyconeAlcoholic and phenolic glycosides (aglycones are alcohols or phenols)Aldehydic G (aglycones are aldehydes).Cyanogenic G (aglycones are nitriles or derivatives of hydrocyanic acid).Anthracene or anthraquinone G (aglycones are anthracene der.).Steroidal G (aglycones are steroidal in nature, derived from cyclopentanoperhydrophenanthrene) .Coumarin G (aglycones are derivative of benzo α-pyrone).Chromone glycosides (aglycones are derivatives of benzo-δ-pyrone)Flavonoidal G (aglycones are 2-phenyl chromone structure).Sulphur containing or thioglycosides(aglycones are contain sulphur).Alkaloidal glycosides (aglycone is alkaloidal in nature) e.g., glucoalkaloids of solanum species. Sugars in glycosides:Monosaccharide (glucose in salicin, rhamnose in ouabain)Disaccharides (gentiobiose in amygdalin).Trisaccharides (strophanthotriose).Tetrasaccharides (purpurea glycosides)Rare sugers (deoxy sugers)Sugar linked in one position to the aglycone rarely in 2 positions as sennosides. DEOXY SUGARSA- 6-deoxy sugars
e.g., 1- methylpentoses
2- α-L-rhamnose.
B- 2,6-deoxy sugars (called rare sugars)e.g.,
1- D.digitoxose 2- D.cymarose C- 2-deoxy sugarse.g.,2-deoxy-D-ribose Characteristic of 2-deoxy sugers:Give positive Schiff’s test for aldehydes.Positive Keller-Kelliani test. PHYSICAL AND CHEMICAL PROPERTIESDiversity in structure makes it difficult to find general physical and chemical properties: 1- A- Most glycosides are water soluble and soluble in alcohols.B- Either insoluble or less soluble in non polar organic solvents.C- More sugar units in a glycoside lead to more solublesolvents.2- Glycosides do not reduce Fehling’s solution, but when areto hydrolysis give reducing sugars (C-glycosides are exceptions).STABILITY AND HYDROLYTIC CLEAVAGE1- Acid hydrolysis:a- Acetal linkage between the aglycon and glyconethat between two individual sugars within the molecule.b- all glycosides are hydrolysable by acids non specific (except C-glycosides).c- Glycosides containing 2-deoxy sugars are more unstablehydrolysis even at room temperature.d- C-glycosides are very stable (need oxidative hydrolysis).2- Alkali hydrolysis:1- mild alkali2- strong alkali3- Enzyme hydrolysis:1- Enzymatic hydrolysis is specific for each glycoside there is a specific enzyme that exerts a hydrolytic action on it.2- The same enzyme is capable to hydrolyze different glycosides,and β sterio-isomers of the same glycoside are usually not hydrolysed by the same enzyme.3- Emulsin is found to hydrolysed most β-glycosideglycoside are attacked by emulsin are regarded as β-glycosides.4- Maltase and invertase are α-glycosidases, capable of hydrolyzingglycosides only. EXTRACTION AND ISOLATION OF GLYCOSIDS:Water mixed with different proportions of methanol or ethanol (most suitable extracting solvent).
Non-polar organic solvents are generally used for de-fating process.Glycosides are not precipitate from aqueous solutions by lead acetate.
GENERAL METHODS OF ISOLATION INVOLVE:1- Destruction of hydrolysing enzymes.Drying for 15-30 min. at 100 C˚.Place plant in boiling water or alcohol 10-20 min.Boiling with acetone.Cold acid pH treatment.Extract at very low temperature.De-fating or purification of the plant material (in case of seedsExtraction of the glycosidal constituents by alcohol, water or dilute alcohols. Some times ether saturated with water for dry material.Concentrate the alcoholic extract (to get rid of the organic solvent). Add water (or hot water)→ filter any precipitate. Purify aqueous extract:Extract non glycosidal impurities by org solvent.Water soluble impurities precipitate by lead acetate. Precipitate excess lead salts. Isolation of the glycosides from the purified aqueous solution, by crystallization. QUALITATIVE TESTING OF GLYCOSIDE: They do not themselves reduce Fehling’s. but reducing sugars upon hydrolysis.To test for the presence of glycosidesEstimate reducing sugars before and after hydrolysis. (by acids or enzymes)TESTS DEPENDING ON THE CHEMICAL NATURE OF THE GENIN:Steroidal or cardiac glycosides:Give positive Liebermann’s test (steroidal structureAnthraquinone glycosides and/or aglycone:Give positive Borntrager’s test, characteristic reddish coloration with alkalies.Flavonoidal glycosides and/or aglycones:Characteristic color with, NH4OH, AlCl3, FeCl3.Cyanogenetic glycosides give upon hydrolysis hydrocyanic acid can be easily tested by change Na bikrate paper (yellow) to red color.Sulphur containing glycosides give black precipitate ofsulphate upon treatment with AgNO3 solution. TESTS DEPENDING ON THE SUGAR PART:
1- Keller Killiani’s test for 2-deoxy sugers:Specificity of action of the hydrolyzing enzymes is often applied for the identification of the sugar moieties of glycosides or even the glycoside as alcohol. 1- Scillarin A [acid hydrolysis] →→→ Scillaridine A + Scillabiose Scillabiose [Scillabiase] →→→ Rhamnose + glucose.2- Prunasin [Prunase] →→→ glucose + HCN + 3- Amygdalin [amygdalase] → Prunasin + glucose 4- Myrosin enzyme is specific for thio D- glucosides e.g.,Sinigrin and sinalbin. SPECIAL TESTS BASED ON THE CHEMICAL STRUCTURE OF THE GLYCOSIDES: Determination of the glycosidic linkages:By the use of α and β glycosidases.By acid hydrolysis of glycosides, immediate optical activity measurement of the resulting solution. Color reactions based on the sugar moiety [2-deoxy sugars]:Keller Killiani:glacialacetic acid containing + FeCl3 + H2SO4 → brown ring free from red (acetic acid a quire blue).2- Xanthydrol:xanthydrol in glacial acetic containing 1% HCl + glycoside [heat]→ red color.N.B. Stability indicating after extraction. U.S.P. Medicinal importance of glycosides:Cardiac drugs: cardiotonic glycosides e.g., digitalis glycosides, strophanthus, squill.Laxatives e.g., anthraquinone glycosides of senna, aloes, rhubarb, cascara, frangula.Counter irritants e.g., thioglycosides and their hydrolytic products ‘allylisothiocyanate’Analgesics e.g., methylsalicylate ‘a hydrolytic product of gaultherin.Anti rheumatic e.g., salicin.Some glycosides are claimed to reduce the capillary fragilityflavonoidal glycosides, rutin, hisperidin.Anti-inflamatory: e.g., the glycoside glycyrrhizin has a demulcent, expectorant and antispasmodic action.
More recently as an anticancer agent e.g., amygdalin known in the U.S. as Laetrile. CARDIAC GLYCOSIDES: 1-The genins of all cardiac glycosides are steroidal in nature, that act as cardiotonic agents.2-They are characterized by theirspecific action cardiac muscle, tone, excitability and contractility of this muscle, thus allowing the weakened heart to functionmore efficiently. All cardio active glycosides are characterized by the following structural features:The presence of β-OH at position C-3, which is always involved in a glycosidic linkage to a mono, di, tri, OR tetra saccharide.The presence of another β-OH group at C-14.The presence of unsaturated 5 or 6- memberedlactone ring17, also in the βconfiguration.The A/B ring junction is usually (cis), while thealways (trans) and the C/D ring junction is in all casesAdditional OH groups may be present at C-5, C-11
1- Cardiac glycosides that α-β unsaturatedlactose ring in position C-17 are known asare represented by thedigitalis and straphanthus2- Digitalis glycosides contain angular methyl group at10, while strophanthus glycoside are characterized by presence of either an aldehydic(CHO) or primary alcoholicgroup at C-10.
CardenolidesDigitalis glycosides R=CH3
Strophanthus glycosides R=CHO OR CH 3- Cardiac agents that have doubly unsaturated 6-membered lactone ring in position C-17as Bufadienolides. 4- This group includes the squill glycosides
Bufotoxin.
Bufadienolides
Squill glycosides R1=OH, R2=HBufotoxin R1 & R2 = ester group 5- The glycone portion at position C-3 of cardiac glycosides may contain four monosaccharide moleculesThus, from a single genin one may have a monoside, a bioside, a trioside or a tetroside. 6- With the exception of D-glucose and L-rhamnose, all the other sugars that are found in cardiac glycosides are uncommon deoxy-sugars e.g., Digitoxose, Cymarose, Thevetose.Digitoxose Cyamarose Thevetose Isolation difficulties:Major difficulty in the isolation of 1ry glycosides from the crude drug.. why? because 1ryglycosides are converted into secondary glycosides by hydrolysable enzymes.Other difficulty is the existence of several closely related glycosides in the same drug, which are extremely difficult to separate and purify.
THE CARDENOLIDESOrigin: D. purpurea, D. lanata, D. lutea and D. thapsi The structures of the common aglycones of thedigitalis group are indicated below:
Compounds R1 R2Digitoxigenin H HGitoxigenin H OHDigoxigenin OH HDX = Digitoxose, DX (AC)=Acetyldigitoxose,G = Glucose.1- Glycosides derived from Digitoxigenin:a- Lanatoside A = Digitoxigenin---DX---DX----DX(AC)---G.b- Acetyl-digitoxin = Digitoxigenin---DX---DX----DX---(AC).c- Digitoxin = Digitoxigenin------DX---DX----DX.d- Purpurea gly A = Digitoxigenin---DX---DX----DX---G
2- Glycosides derived from Gitoxigenin:a- Lanatoside B = Gitoxigenin---DX---DX----DX(AC)---G.b- Acetyl-gitoxin = Gitoxigenin---DX---DX----DX---(AC).c- Gitoxin = Gitoxigenin------DX---DX----DX.d- Purpurea gly B = Gitoxigenin---DX---DX----DX---G 3- Glycosides derived from Digoxigenin:a- Lanatoside C = Digoxigenin---DX---DX----DX(AC)---G.b- Acetyl-digoxin = Digoxigenin---DX---DX----DX---(AC).c- Digoxin = Digoxigenin------DX---DX----DX.d- Deslanoside = Digoxigenin---DX---DX----DX---G The 1ry glycosides Lanatoside A, Lanatoside B, Lanatoside C are acted by specific enzymethe terminal glucose, give the 2ryglycosidesacetylgitoxin and acetyldigoxin respectively. The deacetyl-lanatosides A, B and C can be obtained by the alkaline hydrolysis of the corresponding lanatosides. Digitoxin, gitoxin and digoxin are obtained by the action of alkali on their acetyl-derivatives.SCHEME: COMPLATE B- THE STROPHANTHUS GROUP1- The glycoside K-strophanthosidestrophanthin B (bioside) and cymarin (a monoside)isolated from differentstrophanthus species 2- The 1ry glycoside K-strophanthoside gives by hydrolysis one molecule of glucose and the 2ryglycosideB or K- strophanthin B. 3- The later gives by hydrolysis one molecule ofthe tertiary glycoside cymarin, which on turn hydrolyze into the genin K-strophanthidinand the deoxysugarThe seeds of Strophanthus gratus contains another glycoside named Ouabain or (G-strophanthin),which yield on hydrolysis rhamnose and theaglycone ouabagenin Ouabagenin differs from K-strophanthidin in having 2
additional (OH) groups at C-1 and C-111ry alcoholic group at C-10 instead of the aldehydic
Ouabain (G-strophanthin)
II-THE BUFADIENOLIDESThis group of cardioactive agents includes(the scillarins) and the Toad poison(Bufotoxin). The genins of squill glycosides differ from those of the cardenolides in two important aspects:They have six membered doubly unsaturated lactoneposition C-17.They have at least one double bond in the steroid nucleus.
The Bufadienolides of Squill Name of glycosides StructureGlucoscillarin Scillaridin A ---RH—G---GScillarin A Scillaridin A ---RH—GProscillaridin A Scillaridin A ---RH PHYSICAL AND CHEMICAL PROPERTIES OF GLYCOSIDES:1- SOLUBILITY:
* The different cardiac glycosides show different solubilities in aqueous and organic solvents. They are usually soluble in water or aqueous alcoholthe fat solvents with exception of chloroform and ethylacetate.
* The higher number of sugar units in the molecule, the greater solubility in water but lower soluble in chloroform.
* Alcohols are good solvents for both the glycosides and the aglycones. Therefore, they are considered as the solvents of choice for the extraction of all CG from drugs.
* pet.ether and ether are used for defatting process of drug, they
do not dissolve CG.2- STABILITY:1- Acid hydrolysis cleavage of the glycosides into aglycones and sugar residues.2- Specific enzyme usually coexist with CG in plants, which may split the primary G into G with less sugar unitsdeteriorate during drying and storage unless special precautions are taken. 3- So it is required by many pharmacopoeiascontaining drugs must contain not more than specifiedcontent and that these drugs should be stored in sealed containers overdehydrating agents. 4- It is recommended to heat stabilize these CG, by destroying the enzymes at higher temperatures. At higher temperature, the tertiary OH gp at C-14 may split off as water, leading to formation of an inactive anhydro-form of CG.5- The gitoxin has in addition to tertiary OH at C-14 another secondary OH at C-16. Both OH gps split as water by the action of H2SO4 with the formation ofdouble bonds. These with the double bond of the lactone ring from a conjugated double bond systemcompoundfluorescent in UV light. The detection of gitoxin in other digitalis G is based on the above mentioned reaction. CHEMICAL IDENTIFICATION OF CARDIAC GLYCOSIDESCGs are steroidal in nature, give +Ve withLiebermann’s and Salkoviski’s test. CG that contain deoxy-sugars are distinguished byKiliani’s test, e.g., digitoxose and cymarose. Cardenolides are distinguished from theof color reagents, that are all alkaline solutions of aromatic nitro compounds, namely,
Kedde’s reagent, 3,5 dinitrobenzoic,Raymond’s reagent, metadinitrobenzene,Baljet’s reagent, picric acid,Legal’s test, alkaline solution of sodium nitroprusside All these nitrocompounds react with the the five membered lactone ring (in alkaline medium) to give characteristic colors.
MEDICINAL IMPORTANCECardiotonics, CHF, rheumatic heart disease, atherosclerosis, HTN.Diuretics (capillary of the kidneys are dialated).
SAR:The glycone part displays a great influence on the solubility and the rate of absorption and distribution of the glycosides to the site of action.Small change in the molecules such as a change of the location of the OH gp, modify the cardiac activity or even eliminate it completely. The saturation and/or cleavage of the lactone ring,cardiac activity. Therefore, the closely related CG, differ greatly in the rate of absorption, duration of action and their cumulative effect CARDIAC DRUGS OFFICIAL IN BP &USPdigitalis leaf (digitalis tablets)digitoxin tablets 200μg/tabletdigoxin injection contain 0.0025% digoxindigoxin tablets contain 250μg/tabletgitalin, lanatoside C, deslanoside, strophanthus, strophanthin, ouabain and squill.ANTHRAQUINONE GLYCOSIDE:TYPES OF ANTHRAQUINONE GLYCOSIDE 1- O-glycosides where the aglycone moiety is 1,8 dihydroxyanthraquinone derivatives, e.g., 2- O-glycoside where the aglycone moiety partially reduced 1,8 dihydroxy anthraquinone, e.g., Oxanthrone-type.
Emodin-oxanthrone-9-glucoside
3- C-glycoside where the aglycone structure (anthrone der.) Barbaloin4- O-glycosides where the aglycone moiety is di-anthrone der. (i.e., dimmer) e.g., Sennosides where there isbetween the anthranol units. Sennoside A&B
The most widely used drugs that contain anthracene compounds are:SENNA LEAF:Consists of the dried leaflet ofKhartoum senna, Cassia senna (C.acutifoliasenna (C.angustifolia). Constituents:Dimeric anthracene glycosides derived from two anthrones moieties which may be:
Similar anthrone moiety (Homo-dianthronesanthrone moieties condensate through two C-10 atomes. Thus it can be exist in two optical forms, Sennoside A (L- form) & Sennoside B (meso form).
Sennosides A &B
Or different (Hetero-dianthrones) i.e., one rhein-anthrone & one emodin anthrone, Sennoside C (L- form) and Sennoside D (meso form).
Sennoside C&D
CASCARAThe dried bark of Rhamnus purshiana Family
P. specified that the collection must be made at least one year before the bark is used (fresh bark contains an emetic principle).Constituents:A- Four primary glycosides:1- cascarosides A&B (glycosides of barbaloin)2- cascarosides C&D (glycosides of chrysaloin) B-Two aloins (secondary glycosides):
Barbaloin derived from (C-10-C-glycoside) of aloe-emodin anthrone and chrysaloin derived from (C-10-C-glycoside) of chrysophanol anthrone.C- A number of O- glycosides:e.g., derived from emodin, emodine oxanthrone, aloe emodin and chrysophanol. E- Free anthraquinones:Aloe emodin, chysophanol and emodin. FRANGULA BARK:Frangulin (frangula emodin rhamnoside).Glucofrangulin (frangula emodin glucorhamnoside).hydrolysis of glucofrangulin yields frangulin and glucose.Hydrolysis of frangulin gives frangula emodin and rhamnose. RHUBARBConsist of glycoside of rhein, rhein anthrone, chrysophanol and aloe emodin.Dianthrones of heteroanthrone types are palmidin A, B, C, Rheidins, sennosides A&B and their oxalate esters (sennosides E&F).The presence of tannins in rhubarb makes the drug constipating. So in small doses, rhubarb exerts no purgative action but acts only as intestinal astringent, but large doses USES:Cascara is a purgative, mainly in the form of liquid extract, elixir or as tablets prepared from a dry extract. The laxative action of the crude drugs is always higher than from their content of anthracene der. The different anthracene der. contained by the crude drug are said to exert asynergistic action.Thus, the naturally occurring anthracene glycosides were found superior to thesynthesis of numerous hydroxyl anthracene der. Some of these synthetic compounds act too drastically and also caused kidney damage.The only compound which is used to some extent in current medicine is danthrone. It is also used as a standared in
colorimetric assays of anthraquinone glycosides.Danthrone
Note:The 1ry glycosides are more active than the aloins while the free anthraquinon have little purgative activity. C-C glycosides, aloins are very resistance to hydrolysis and are not easily hydrolysed (like other anthrones and anthranols) to corresponding anthraquinones.Aloin type glycosides are present in aloes and other anthracene bearing drugs of the family liliaceae. SARGlycosilation:The purgative action of anthracene bearing drugs is owed to their anthracene glycosidal content rather than their content of free anthracene aglycones (i.e., glycosylation is the main requirement for activity, as the sugar moiety serve to transport the aglycone to the site of action in the large intestine). Hydroxylation:Hydroxylation of C-1, C-8 is essential for activity. Increase hydroxylation leading to increase solubility. Oxidation level:The degree of oxidation at positions C-9 & C-10 plays an important role in the pharmacological activity. Higher oxidation level at C-9 & C-10 caused lowering of activity. i.e., anthrones and anthranols are more potent than their corresponding oxanthrones, which in turn more active than their corresponding anthraquinones. Complete reduction of C-10 &C-9 lead to complete loss of activity.The nature of substances at C-3:Derivative with CH2OH (as in aloe emodin) are more active than those with CH3 substitution. The latter more active than derivative with COOH substitution at C-3.Anthraquinone glycosides containing adimer more active than a monomer.
Effect of storage on the active of anthracene glycosides: Prolonged storage of anthracene bearing drugs may bring oxidation of anthranols and anthrones to give theactive anthraquinones. Thus, the activity of drugs decreases by time. However,anthraquinone glycosides do not cause anygriping action (like anthranol and anthone)antispasmodic such as belladonna is prescribed with them. Drugs as senna, Aloe and cascara preparationsactivity for a long time. Cascara and frangula must be aged for one yearfor medicinal preparation.WHY? Stability is achieved as follows:1- In senna, there is dimeric glycoside in which a C-C bridge between two anthrone units is formed (the C-10 position of one anthrone is involved in a C-C-covalent bonding with C-10 of the other anthrone). Thus, the C-10 position can not be easily oxidized and the anthrone structure is stabilized. 2- In the aloe, the aloins (barbaloin & chrysaloin) contain C-C glycosidic linkage (anhydroglycosides) stabilise the anthrone structure. In cascara, cascarosides have an additional O-glycosidic linkage (beside the C-10-C glycosidic linkage. The solubility of cascarosides is increased and thus, produce higher pharmacological activity. PROPERTIES OF ANTHRAQUINONE DERIVATIVES:The glycosides are extracted and hydrolyzed by boiling the drug with acids.The aglycones are extracted from the acidic solution with ether or benzene. Upon shaking the ether or benzene layer with aqueous alkali or ammonia solution, the aqueous layer assumes a deep red color, because of the formation of anthraquinone salts.Borntrager’s reaction can distinguish anthraquinones from anthrones and anthranols whichdo not give the test unless they are converted to anthraquinone by oxidation with mild oxidants
such as hydrogen peroxide or ferric chloride. Official anthraquinone drugs in B.P and U.S.P.:Senna leaf & senna fruit (pod).Aloes.Cascara tablets, elixir, dry exract, liquid extract.Rhubarb powdered, tincture.DanthroneFrangul bark
FLAVONOIDAL GLYCOSIDES Flavonoidal compounds are considered as the largest group of naturally occurring phenols.Flavonoidals constitute the majority of the yellow colored plant pigments.Many flavonoidal compounds present as a glycosidic or as a free forms.All derived from the same parent nucleus, 2-phenyl-benzopyran (flavan), thus they have a basic C-15 skeleton. Flavonoidal compounds are classified according to the oxidation level of central pyran ring they are classified into flavones, isoflavones, flavonols,flavanonesflavanoids) anthocyanidins,chalcones and True flavones, are 2-phenyl chromonesbenzopyrone), while isoflavones are 3-phenyl chromones Flavonols are 3-hydroxyflavones, while flavanones are 2dihydro der. of flavones (2,3-double bond is lacking (2-phenylbenzopyran) (2-phenylbenzopyr Anthocyanidines, chalcones and aurones are lack the typical flavone structure. Anthocyanidins and its glycosides (anthecyanins) are ionic oxonium salts. This is responsible for the permanent blue, purple, violet, mauve, and red color of flower, fruits and leaves of higher plants.
Anthocyanidins and anthecyanins are soluble in polar solvents. Cyanidin chloride is an example of anthocyanidines .Chalcones, have no central pyrone ring, so they are notflavonoidal compounds. The parent compound chalcone, is chemically phenyl-styryl ketone, or benzylidene acetophenone. Aurones are oxidized forms that are obtained by enzymatic oxidation. Instead of the central pyrone ringflavonoidal structure, auroneshave five membered ringChalcon Aurone PROPERTIES OF FLAVONOIDS Flavonoids dissolve in alkalis give intense yellow color solution, on the addition of acid become colorless. Flavonoids exhibit strong fluorescence under UV light. Flavonoidal glycosides are soluble in water and alcohol. Ethylacetate is the solvent of choice for the extraction of flavonoids from aqueous solution. Flavonoids compounds may be characterized through the investigation of their UV Spectra, that usually showmain bands, 1- Band at higher wavelength (band I) which is attributed to the cinnamoyl fraction of the flavonoidal structure 2- Band at lower wavelength (band II)the benzoyl fraction of the flavonoidal structure.STRUCTURE: COMPLETEBand I >> 300 nm If R= H R=OH Flavones flavonols Band I: 304-350 nm Band I: 352-385 Band I: 328-357
Band II << 300nm(250-280 nm)Note:More OH in ring A: Bathochromic shift in band II.More OH in ring B: Bathochromic shift in band I.Shift reagents:Back to lab.EXAMPLE OF FLAVONOIDS GLCOSIDES1- Diosmin: flavone glycosideOccurance: buchu leaves, Barosma crenulataUses: diuretic and diaphoretic action of the leaves is owed in part to diosmin, and in part to diosphenol, the main constituent of the volatile oil of the leaf. Diosmin Upon hydrolysis, diosmin yields rhamnose, glucose and diosmetin. 2- Rutin and quercetrin: are examples of flavonol glycosides a- Rutin occurs in the leaves of buckwheat. It is the 3-rhamnoglucoside (called rutinose) of the genin quercitin. It gives on hydrolysis the aglycone (quercitin)molecule of glucose, and one molecule of rhamnose.Rutin is used to1- Decrease capillary fragility.2- It is a biflavonoids that plays a true vitamin function. b- Quercitrin is quercitin 3-O-rhamnoside.It occurs in the bark of Quercus tinctoria.Quercitrin yield upon acid hydrolysis rhamnose and quercetin. The aglycone quercetin occurs in bearberry leaves (Uva Ursi) and has a diuretic action of the leaves. 3- Hesperidin: it is an example of flavanones. It is the main flavonoidal glycoside of citrus fruits.
Upon hydrolysis by acid, hesperidin givesand hesperitin.Uses:1- Hesperidin appears to be identical to vitamin P (citrin).2- It is necessary for absorption and retention of vit C that lead to decrease capillary fragility.3- Decrease CVD and HTN. Uses of flavonoids:Increase capillary resistance and decrease vitamins C & P deficiency.They are recommended in the treatment of thrombopenia (blood coagulation).They are reported of value in the treatment of influenza, when given with ascorbic acid. Isoflavone:Genistein show significant oestrogenic activity.Rotenoids employed as insecticide.
Flavono-lignans Coupling of a flavonoid moiety with hemi-lignan molecule by oxidative coupling. SILYMARINE The leaves and fruits of Silybum marianumcontain silymarin (silybin).1- Silymarin is a very effective lipotropic and hepato protective therapy.2- It is a free radical scavenger. 3- Supportive treatment of acute and chronic alcoholic poisoning and toxin induce hepatitis. 4- It is used for treatment of liver cirrhosis caused by plant toxins (mushroom, amanita), silymarin is applied as intravenous injection. 5- Silymarin is available in the market in the form of tablets, effervescent granules. Trade name legalon, silyhexal, silirex…
etc.
Synthetic flavonoids Flavoxate:Uses:To remove pain (anti-spasmodic) and anti-inflammatory of the genitor urinary tract. Flavoxate tablets are available under several names: Urispas, Uronid, Spasurit, Genurin). SAPONINS* Saponins are a group of amorphous colloidal glycodides which is wiedly distributed in the higher plants. * Have ability to form lasting foam when shaking in aqueous solution. * They are excellent emulsifying agents (modify surface tension). * Formerly used as detergents to replace soap (e.g., quillaia). * Saponins are colorless and optical active. They form colloidal solution with water and are soluble in alcohol and dilute alcohols. * Saponins have haemolytic properties, they precipitate the cholesterol and lethisins that exist in the memberanes of the red blood cells and thus haemoglobin is liberated. So, saponins are extremely toxic when injected into the blood stream. However, they are not harmful when taken orally. * Saponins are difficult to purify. However, they precipitated from solutions containing them by the addition of a solution of the sterol, filtering off the insoluble sterol-saponin
compound and boiling it with toluene which resolves the compound again into sterol (which is soluble in toluene) and saponin (which is insoluble in toluene).Chemically:Saponins are classified according to the genin part into:1- Steroidal type C25.2- Triterpinoidal type C30.Both types of saponins have the glycosidic linkage at Medicinal importance of saponins: The steroidal saponins are structurallysynthetic compounds that have a therapeutic significance, such asadrenocortecoids and the sex hormonessuitable precursors in the partial synthesise.g., Diosgenin(sapogenins) isolated from the rhizome ofDioscoria species. Saponins increase the rate of absorption of many pharmacological active substances (e.g., cardiac glycosides). Many saponin-containing drugs are used asIpeca, Senaga and liquorice) as their contents ofstimulate bronchial secretion and also activate the ciliary epithelium of the bronchi. a-The triterpenoidal saponin glycoside,glycyrrhizin,sweet principle ofliquorice. It is calcium and potassium salts of glycyrrhizic acid, which in tern is theacid glycoside of glycyrrhitinic acid. b- Beside being a valuable flavouring and sweetening agent, liquorice has demulcent, expectorant and antispasmodic action. All these activities attributed to the saponin, glycyrrhizin. c- Recently, glycyrrhizin was shown to be effectively in gastric ulcer treatment and have a cortisone like action in rheumatic arthritis and other inflammatory diseases.
Saponins drugs officially in the B.P and U.S.P:1- Quillaia bark: used as emulsifier.2- Liquorice root: used as flavouring agent and expectorant. TANNINS1- Tannins are widely distributed phenolic plant constituents.It is characterized by being able to combine with proteinsanimal hides thus preventing theirputrefactionthem into leather (true tannins). 2- Tannins are detected qualitatively byGoldbeater’s skin test (tanning test), and can bequantitativelyby absorption on standard hide powdermolecular weight tannins that are capable of It is more acceptable to define true tannins as those high molecular weight phenolic plant constituents that can be detected by Glodbeater’s skin tanning test. 3- True tannin solutions have the ability of precipitatingproteins (gelatine), heavy metals, alkaloids and glycosides 4- This will exclude simple molecular weight compoundsas gallic acid, catechin, flavan-3,4-diol and chlorogenic acidthat usually coexist with true tannins. These simpler tannins like compounds are referred to aspseudotannins. TRUE TANNINS ARE DISTINGUISHED INTO TWO MAIN CLASSES: Hydrolysable tannins Condensed tannins 1- Hydrolysable tannins:a- These can be hydrolyzed by acids or enzymes to give phenolic acids (gallic or ellagic) and glucose, so called phenolic acid glycosides.b- Tannins of gallic acid are called gallitanninsof ellagic acid is called ellagitannins.c- Dry distillation of hydrolysable tannins gives pyrogallol. This
class is named pyrogallol tannins.d- Gallitannins and ellagitannins react with ferric salts to give bluish color precipitate. 2- Condensed tannins:a- These are more resistant to hydrolysis upon prolonged heating with acids.b- They undergo decomposition (not hydrolysis) to give a red soluble compound (phlobaphane).c- Condensed tannins are derived from catechin and flavan, 3,4-diol.d- Dry distillation of condensed tannins gives catechol. This class is named catechol tannins.e- Being phenolic, it reacts with ferric salts to give greenish color precipitate. ALCOHOLIC AND PHENOLIC GLYCOSIDES1- Salicin:Salicin is classified as:1- Alcoholic glycoside, as it contains freegroup.2- A phenolic glycoside, as its aglycone is phenolic Salicin PROPERTIES OF SALICIN:Salicin is obtained from different species of Salix, the principle commercial source is Salix fragilis.Salicin is used for many years as a remedy in the treatment of fever and rheumatism.It is now used as an analgesic-antipyretic in case of periodic fever. It is better tolerated in the stomach than sodium salicylate, asprin and other antipyretics and anti-inflammatory agents, which have largely displaced in medical practice.Salicin is hydrolyzed byenzyme emulsininto saligenin (Salicyl alcohol)Acid hydrolysis of salicin givesphenolic ether called saliretin which is a condensation product of two molecules ofsaligenin.Oxidation of saligenin gives salicylic acid and this accounts for
the medicinal value of salicin. ARBUTIN1- Arbutin is a phenolic glycoside that occurs in bearberry leaves Arectostaphyllos uva ursi.2- When hydrolysed with acids or with emulsin it yields glucose and hydroquinone.3- It is used as diuretic and also has bactericidal action. This activity is due to the hydroquinone given by hydrolysis.4- Uva ursi leaf contains also methylarbutin (the methyl ether of arbutin), that also contributes to the diuretic and urinary antiseptic action of the leave. ALDEHYDE GLYCOSIDESGLUCOVANILLIN:Glucovanillin is a glycosidal constituent of green vanilla pods.The fruits of the plant (pods) are collected and carefully cured. To permit enzymatic action on the glycoside with the liberation of vanillin (the aglycone) which is the principal flavouring constituent of the pods.Vanillin is widely used as a flavouring agent. It may be obtained from vanilla pod or prepared from the glycoside coniferin, lignin or from thephenolic volatile oil constituents eugenol.
From Coniferin and lignin From Eugenol The bulk of vanillin which is produced commercially is prepared from lignin, which gives upon hydrolysis coniferyl alcohol. Lignin is obtained in extremely large amounts as a by product of timber industry.CYANOGENIC GLYCOSIDES1- These are glycosides that are yield hydrocyanic acidof their hydrolytic products.2- Plant containing these glycosides are toxic.
3- The aglycone part is cyanohydrin of a carbonyl compound (condensation product of HCN with analdehyde or keton4- The majority of cyanogenic glycosides are derived of benzaldehyde cyanohydrin. AMYGDALIN
D-Mandelonitrile gentiobiosideAmygdalin is the most widely distributed cyanophore glycoside.It occurs in several Prunus species, and is obtained from bitter almonds (Prunus amygdalus Var. amara Family Rosaceae).Amygdalin is considered as gentiobioside of D-mandelonitrile. Gentiobioside is a reducing disaccharide consisting of two molecules of β-glucose linked bylinkage.
Acid hydrolysis of amygdalin split two molecules of glucose and one molecule of mandelonitrile. The latter decomposes spontaneously to form benzaldehyde and HCN.Different enzymes act upon amygdalin in different ways: DETECTION OF CYANOGENIC GLYCOSIDESThe plant material is cutted into small fragments and then a filter paper moistened with sodium picrate is then suspended in the neck of the flask, the flask is stoppered and incubated in a warm place (40˚C) for about 30-60 min. By this time, theenzymes act upon the glycosides with the liberationHCN which turns, the sodium picrate paper convert to brick red color. SULPHUR CONTAINING GLYCOSIDES: Thioglycosides 1- A number of plants of the family Cruciferaecontaining sulphur.2- Hydrolysis of these, yieldgenins ofthiocyanate structure e.g., mustard oils.3- The best known compounds Sinigringlycosides occurring in black mustard andrespectively.
4- The glycosides and their specific enzymes are found in different cell in the seeds. They donot interact until they are brought together by the distruction of the cell walls. 5- The general structure of thioglycosides is: 6- The anion is called the glucosinolate ionor aromatic. The cation (X) may be asimple metal iona complex organic cation, e.g., sinapine ion of sinalbin7- Sinigrin gives upon hydrolysis, glucose, allylisothiocyanate (volatile oil of mustard) and potassium acid sulphate.8- Hydrolysis of the glycoside sinalbinisothiocyanate (Acrinyl isothiocyanate), glucose and the acid sulphate of a quaternary alkaloid,sinapine.9-Black and white mustard seeds are used as rubefacients and counter irritants. These effects are attributed to their contents of thioglycosides. COUMARIN GLYCOSIDES: Aglycone 1- coumarin (benzo-α-pyrane).2-coumarin derivative (hydroxyl and methoxy coumarins).Umbelliferone [7-hydroxy coumarin] is the lactone of umbellic acid which occurs both in the free state and in the form of glycosides in someresins of the Umbelliferae (galbanum).Coumarin and its derivatives give blue or violet fluorescence in aqueous ammonical solutions (conjugated double bond system). This is made use of in qualitative testingcoumarin derivatives and coumarin glycosides and drugs containing them. The oleo gum resin galbanum that contains umbelliferone in a free state is distinguished from asafoetidaonly combind umbelliferone, by the addition of ammonia to its aqueous alcoholic extract, when the characteristic blue fluorescence is given. Asafetida responds positive to the fluorescence test only after acid hydrolysis.
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