Glycosides

1
Glycosides

• Definition
• Organic natural compounds present in a lot of
  plants and some animals, these compounds upon
  hydrolysis give one or more sugars (glycone)
  ß_form and non sugar (aglycone) or called genin.

2

• 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.

3

• Separation between glycosides parts
• Glycosides glycone aglycone HCL
• G A saltH2O
  
• (H2OG)A (H2OG)(chloroformA)
• 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 HCLdil
Neutralization by Using alkaline
Filtration
chloroform
4

• Note
• Alcohol and acetone are water miscible
  compounds,so we can't use them as organic
  solvents for aglycone separation.

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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).

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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.

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Biosynthesis of glycosides(O-glycosides)

• UTP(Uridine Triphoshate) sugar-1-phoshate
  UDP-sugar ppi(Pyrophosphate
  inorganic).
• UDP-sugar acceptor (aglycone)
• Acceptor-sugar UDP

Uridylyl transferase Enzyme
Glycosyl transferase Enzyme
Glycosyl transferase Enzyme
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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).

9
Cont

• Some glycosides have antibacterial activity, so
  they protect the plants from bacteria and
  diseases.

bacteria
kill
Bitter almond
HCN
hydrolysis
Amygdalin
Eomlsin enzyme
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Classification of glycosides
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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- ConvollosideConvallaria majalis Lily of
  the Valley.

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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).

13
Cont

• 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
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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.

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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.

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N.B C-glycosides are not hydrolyzed by acids or
alkalis or by enzymes mainly . 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 (-SCN-)
(SCN) 6-anthracene -------gt 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 .
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Most of glycoside may be named according to the
plant from which they isolated for
example 1-salicin salix- 2-cascaroside
_cascara 3-aloin- Aloe vera 4- sennoside
senna- 5-frangulin frangula 6- glycyrrhizin
glycyrrhiza And others. 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 1-drying the plants fresh in special oven
at 100 c for 30 minutes. 2-boiling them with
organic solvents for 20 minutes 3- boiling them
with acetone 5 minutes N.B. If present in this
plant tannins or resins we add lead acetate to
precipitate them.
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• Classification of glycosides according to a
  glycone part.
• 1- phenolic group of glycosides-
• Such as arbutin which isolated from bearberry
  leaves
• Uses UTI as antiseptic and antibacterial mild
  diuretic
• Drugs
• -Esoterica cream age spots
• -hydroquinone solution wet hands
• 2- saponin group of glycoside
• Important group of glycosides which widely
  distributed specially in the higher plants parts
• b. Most of them are neutral compounds, soluble in
  water insoluble in the organic solvents.
• d. Irritant compounds for mucous membranes
• e. They form with hydrolysis glycone part which
  usually ß-D-glucose or its acids (glucuronic
  acid) Sapogenin

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f. Their aqueous solutions from froths (foam) on
shakin and form emulsions on shaking and heating
with oils and fats g. They destroy RBC
(corpuscles) specially for fish and cold blooded
animals m. Sapogenin (Triterpenoid) divided to
1- steroidal Sapogenin 2- pent acyclic
Sapogenin Examples- licorice roots contain
saponin glycoside which called Glycyrrhizin Glycyr
rhizin hydrolysis glycyrrhetic acid
Z.M. glucyr acid Sweet taste solution in
H2O bitter taste
insoluble in H2O
expectorant
anti-inflammatory

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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
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• 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.

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• 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.

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• 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.

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• 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

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

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• 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

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• 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.

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• 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 .

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• 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

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• Organic sulfur drugs
• Garlic cloves
• Characteristic odor of Garlic
• Allicin yellow liquid responsible for the odor
  of Garlic.
• Uses
• 1.Anti-bacterial
• 2.Anti-hyperlipidemic activity HDL
• 3.anti-histaminic
• 4.anti-coagulant
• 5.Immune system stimulant.
• Coated tablet and capsules stomach acid
  inactivates alliinase enzyme.

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• 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

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• 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.

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• 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

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• Anti spasmodic activity like Thyme and sage
  flavonoids.
• Cytostatic activity.
• Classification of Flavonoids according to the
  main nucleus

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• C.G (Cardiac glycosides) group of
  glycosides which has powerful action on
  
  cardiac muscles (cardiac muscle
  stimulant).
• C.G glycone part consist of one , two,
  three monosaccharide units or more similar or
  different
• Aglycone part has steroidal nucleus
• 
  cyclopentanoperhudrophenanthrene
• B. glycone part of C.G always attached at C-3
  position of aglycone part
• classification
• 1. cardenolide (one double bond, lactone ring)
• Has five member lactone ring (unsaturated)
  attached at C17 B position of steroidal
  nucleus.

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• 2. Bufadienolide (contain two double bonds,
  lactone ring)
• Has six member ( unsaturated ) lactone ring
  attached at C-17 alpha position

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• What is important for activity of C.G -
• 1) The presence of hydroxyl group in C14 position
  makes the glycoside very active and gives rapid
  action in the body, but if we change it to (H)
  group the drug will be inactive or less
  active.
• 2) The presence of Alpha Beta unsaturated
  lactone ring increases the activity of C.G, but
  if we make it saturated the C.G will
  lose its activity.
• 3) The ring junctions Cis, Trans, Cis make the
  nucleus very stable so more active.
• 4) The sugar part increases absorption and
  distribution of C.G in the body
• S.P Glucose, Rhamnose, Cymarose, Digitoxose

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• Examples of Cardenolides
• 1) Digitalis glycosides
• Digoxin
• Digitoxin
• Gitoxin
• 
  

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• 2) Strophanthus gratus C.G
• Oubain

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• 3) Strophanthus Kombe glycoside
• K- strophanthin

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• Bufadienolide example
• Squill bulb glycoside
• Scillaren

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• Chemical tests -
• 1) Keller Kiliani test C.G CH3COOH H2SO4
  FeCl3 brown
• 2) Legal test C.G pyridine sodium
  nitroprusside Red to pink colour
• Uses 1-CHF 2- arrhythmias
• General properties of C.G 1- Amorphous
  powder 2-bitter taste
  
  
• 
  3- sol. In H2O
  4-Insol. In Org. solvents
• 
  5- Very toxic compounds 6- Odorless
• dig.
  Bind specific antibody

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Tannins
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• Complex natural organic compounds, polyphenolic,
  polyhydroxy benzoic acid derivatives or Flavanol
  derivatives.
• Widely distributed in the nature (leaves, barks,
  immature fruits but, they disappear during
  ripening process).
• They protect the plants from herbivorous
  animals, insects, bacteria and others specially
  during growth, like in new leaves which contain
  high percentage of tannins.
• Some of them have low molecular weight but, most
  of them have very large molecular weight.

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Physico_chemical properties

• They form colloidal solutions with water.
• Non crystalline substances.
• Their aqueous solution is acidic.
• They have sharp puckering taste.
• They have astringent property.
• They precipitated by alkaloids, gelatin, salts
  of heavy metals, proteins (enzymes).

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• Tannins are classified into
• True tannins (hydrolysable) (non-hydrolysable).
• 2. Pseudo tannins.

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• Classification of tannins
• True tannins
• Hydrolysable group
• 1- Hydrolyzed by acids or enzymes (Tannase).
• 2- They are esters of a sugar (ß-D-glucose) with
  one or more trihydroxybenzene carboxylic acid.
• 3-The tannins which derived from Gallic acid
  called Gallo-tannin or glucogallin like in
  Rhubarb rhizomes, Clove buds, Bearbers leaves.

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4- tannis which derived from ellagic acid called
ellagotannin or glucoellagin like in Pomegranate
roots bark and Eucalyptus leaves (which also
contain Tannic acid which is Gallotannin). 5-
They form (H.T) with FeCl? dark blue color. (b)
Non hydrolysable group of tannin, condensed
tannins or called proanthocyanidin tannins 1-
has resistance to hydrolysis by acids or
enzymes. 2- they are Flavanol derivatives
1) Flavan-3-ol like catechin 2)
Flavan-4-ol like leucocyanidin
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3- they are founded In barks like Cinnamon
(Phlobatannins), Cinchona (Cinchotannin), Wild
cherry. In seeds Cacao, Cola (Colacatechin). In
leaves Tea. 4- they produce dark green color
with FeCl?. 5- they produce Catechol with
HCl(conc.) and with vannillin_HCl reagent.
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2) Pseudo tannins 1- they have low
molecular weight. 2- they occur as
Gallic acid like in Rhubarb rhizomes. as
catechin like in Cacao, Acacia. as
chlorogenic acid like in coffee.
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• The general uses of tannins
• Anti diarrhea .
• Anti bacterial .
• Antidote in case of poisoning from alkaloids and
  heavy metals .
• Haemostatic .
• Mild diuretic .
• Leather industry .
• Astringent for inflammated mucous membrane
• Stomachic .

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• Chemical tests
• With FeCl?
• (a) H.T? dark blue
• (b) Non H.T ? dark green
  
• 2) ppt. with alkaloids, gelatin, proteins, and
  salts of heavy metals like lead acetate, copper
  acetate.
• 3) With H2SO4 ? yellow
• 4) Vanillin_HCl reagent ? red to pink color.