Pharmacognosy | Glycosides

Glycosides

• Sugar ethers;

• heteropolysaccharides

• compounds that yield one or more sugars among the products of hydrolysis.

Glycoside — general structure

R1-O-R2

Glycoside — R1

• glycone

• Sugar portion of a glycoside;

• composed of different sugars (heteropolysaccharides).

Glycoside — R2

• Aglycone/Genin

• Non-sugar portion of a glycoside

Glycoside — Glycosidic bond

Connects the sugar and non-sugar portion and can be hydrolyzed by acids or enzymes.

Glycoside — Formation of a glycosidic bond

Hydroxyl of the sugar portion is condensed with a hydroxyl group of the non-sugar portion.

Glycoside — Glycoside configurations

Both α and β glycosides are possible; only β form occurs in plants.

Glycoside biosynthesis — aglycone

Aglycones are too different to be generalized; two important pathways include the mevalonate pathway and shikimic acid pathway.

Glycoside biosynthesis — glycone

Glycone comes from photosynthesis.

Glycoside biosynthesis — Actual glycoside formation

Formation of UDP-sugar followed by condensation with the aglycone.

Tannins — biosynthesis

Tannins are also from the shikimic acid pathway.

Two important biosynthetic pathways related to glycosides

Mevalonate pathway and shikimic acid pathway.

3-Dehydroshikimic acid

Precursor of shikimic acid.

Shikimic acid pathway

• Gives rise to aromatic amino acids.

• branches: Prephenic acid and chorismic acid

• shikimic acid: Plant acid derivative of all aromatic compounds.

Prephenic acid vs. chorismic acid

They differ in the location of the CH2COCOOH substituent; C1 for prephenic acid and C3 for chorismic acid.

Prephenic acid branch

Can give rise to phenylpropanoids; shortcut: C6-C3.

• Many glycosides and volatile oils are classified as phenylpropanoids.

Prephenic acid — products (3)

Aldehyde, lactone, flavonoid.

Chorismic acid products — amino acids

Anthranilic acid and amino acid (serine).

Prephenic acid products — amino acids

Phenylpyruvic acid becomes phenylalanine; p-hydroxyphenylpyruvic acid becomes tyrosine.

Coumaric acid

Produces lactone glycosides.

Gallic acid

From dehydroshikimic acid; produces hydrolyzable tannins.

Coumaric acid

• produces chalcones, which produce flavonoids.

• Flavonoids are required for production of condensed tannins, which is why flavonoid glycoside is linked to condensed tannins.

Mevalonate pathway

Acetyl CoA becomes HMG CoA through HMG CoA reductase, then becomes mevalonic acid.

Mevalonic acid pathway — products (2)

Saponins, cardiac glycosides

Other glycosides (3)

Cyanophores, glucosinolates, and miscellaneous glycosides.

Other products of the mevalonic acid pathway

Hormones, cholesterol, and fat-soluble vitamins (ADEK).

Shikimic acid pathway — product apart from CAPA and PALF

Lignans

Chorismate branch — glycosides (3)

Anthraquinone glycoside, phenol, alcohol.

Anthraquinone glycosides — use

Stimulant cathartics except for chrysarobin.

Anthraquinone glycosides — MOA

Increase tone of smooth muscle in the wall of large intestines and inhibit Cl ion channel.

Anthraquinone glycosides — aglycones (4)

Anthracene derivatives such as chrysophanol, emodin, aloe-emodin, and rhein.

Chrysophanol — sources (2)

Anthraquinone aglycone found in rhubarb and cascara.

Emodin — sources (2)

Anthraquinone aglycone found in rhubarb and cascara.

Aloe-emodin & Rhein — sources (2)

Anthraquinone aglycone found in rhubarb and senna.

Anthracene

3 fused rings

Anthraquinone derivatives — color

Orange-red colored compounds.

Anthraquinone derivatives — solubility

Soluble in dilute alcohol and boiling/hot water.

Anthraquinone derivatives — with a base

Give a characteristic red, violet, or green color with NH3 or NaOH.

Anthraquinone derivatives — types (5)

1. Anthraquinone

2. Anthranol/Anthrone

3. Diantrones

4. Oxanthrone

5. Aloin type/ C-glycoside

Anthraquinone

2 =O groups; anthracene derivative

Anthraquinone — types (2)

1. Dihydroxy phenol

2. Trihiydroxy phenol

Anthraquinone — dihydroxy phenols (4)

chrysophanol, rhein, aloe emodin, physcion

Anthraquinone — trihydroxy phenols (2)

emodin, emodic acid

Anthrone

1 =O group.

Anthranol

1 -OH group.

Anthranol/Anthrone — example

Chrysarobin

most reduced type of anthraquinone

Anthranol — distinction

Oxanthrone

1 -OH and 1 =O

Oxanthrone — example

Emodin

intermediate between anthraquinone and anthranol

Oxanthrone — distinction

Dianthrone

Two molecules of anthrone.

Dianthrone — examples

• Senna

• Cassia, Rheum, Rhamnus

• high cathartic effect

Aloin type/C-glycoside

Cascara sagrada (main constituent: barbaloin)

Borntrager's test

Test for anthraquinone glycosides involving extraction using organic solvent followed by addition of base.

Borntrager's test — positive result

Red color on the lower alkaline layer.

Borntrager's test — negative result

Indicates a very stable form of anthraquinone, especially reduced types of anthranol; sample must be hydrolyzed and oxidized first.

Modified Borntrager's test

Presence of a very stable type of anthraquinone; Uses additional ferric chloride/peroxide to force oxidative hydrolysis.

Modified Borntrager's test — positive result

Pink or red color in the alkaline layer.

Borntrager's tests — Anthranol

Anthranol: negative Borntrager's test but positive modified Borntrager's test.

Anthraquinone glycosides (7)

1. Sacred bark

2. Frangul

3. Aloe

4. Rhubarb

5. Senna

6. Goa

7. St. John’s Wort

Sacred bark — synonym

Cascara sagrada

Sacred bark — source

Dried bark of Rhamnus purshianus.

Sacred bark — family

Rhamnaceae.

Sacred bark — constituents (2)

1. Cascarosides A and B, optical isomer of barbaloin;

2. Cascarosides C and D, optical isomer of chrysaloin.

Sacred bark — uses (2)

Cathartic for habitual constipation; restores natural tone of the colon.

Sacred bark — Casanthranol

Purified mixture of the anthranol glycosides; combined with surfactants or hydrocolloids.

Sacred bark — aging

Should be aged for at least 1 year prior to use.

Sacred bark — curing

To reduce bitter taste, cure with MgO or alkaline earths.

Frangula — synonym

Alder buckthorn

Frangula — source

Dried bark of Rhamnus frangula.

Frangula — family

Rhamnaceae.

Frangula — constituents (2)

Frangulin and glucofrangulin.

Frangula — use

Cathartic.

Aloe — synonym

Sabila

Aloe — sources (2)

Dried latex leaves of Aloe barbadensis and Aloe spicata.

Aloe — family

Liliaceae.

Aloe — constituents (2)

Barbaloin (aloe-emodin anthrone) and chrysophanic acid.

Aloe — use

Cathartic (drastic); used for compound benzoin tincture.

Aloe — preparations (2)

Aloe vera gel; stabilized aloe

Aloe vera gel — uses (5)

Treatment of burns, abrasions, skin irritations, purgative, and alopecia (BASPA).

Stabilized aloe — use

Used for lotion or yogurt production.

Rhubarb — synonyms (2)

Rheum/Chinese rhubarb

Rhubarb — sources (3)

Rheum officinale, R. palmatum, and R. raponticum.

Rhubarb — family

Polygonaceae.

Rhubarb — constituents (3)

Rhein anthrones (2.2%), glucorhein, and glucogallic acid.

Adulterant from rhapontic rhubarb; shows blue fluorescence, absent for other rhubarb.

Rhaponticin

Rhaponticin — scientific name

Rheum rhaponticum

Senna — synonym

Slimming tea

Senna — sources (2)

Dried leaflets of Cassia angustifolia and Cassia acutifolia.

Senna — species (2)

Tinnevelly senna; Alexandria senna

Tinnevelly senna — source

Cassia angustifolia

Alexandria senna — source

Cassia acutifolia

Senna — family

Fabaceae.

Alexandria senna — determination

Pink with MgOAc in daylight;

green-orange in filtered UV.

Tinnevelly senna — determination

Orange with MgOAc in daylight;

‘yellow-green in filtered UV.

Senna — constituents (2)

1. Sennosides A and B are major;

2. sennosides C and D are minor.

Senna — aglycone

Sennidin A and B.

Senna — use

Very potent cathartic

Senna — potency

more potent than cascara sagrada; due to dianthrone structure

Senna — cultivation

Cultivated on wet lands resembling rice paddies, as successor to rice.