-

GLYCOSIDES AND TANNINS

Yield one or more sugars among the products of
hydrolysis
-D-glucose -> most frequently occurring sugar
Glucose = glucoside = glucoside
GLUCOSIDE
- acetals
- hydroxyl of the sugar is condensed with a
hydroxyl group of the non sugar component
- second hydroxyl: condensed within the sugar
molecule itself to form an oxide ring
Glycosides may be considered sugar ethers
Aglycone: nonsugar component
Glycone: sugar component
- alpha and beta glycosides are possible
- depends on the stereoconfiguration of the
glycosidic linkage
Emulsin and most other natural enzymes
hydrolyze only the beta varieties
Important roles:
- regulatory
- protective
- sanitary function
D-glucose -> most common sugar
All natural glycosides are hydrolyzed into a
sugar and another organic compound (by boiling
with mineral acids)
Emulsion (of almond kernels) and myrosin
(black mustard seeds) each hydrolyze a
considerable number of glycosides
Glycosides that are derivatives of rhamnose
require a special enzyme -> rhamnase

BIOSYNTHESIS OF GLYCOSIDES
2 parts:
- general reactions couple a sugar residue to an
aglycone
Principal pathway of glycoside formation
- transfer of a uridylyl group from uridine
triphosphate to a sugar 1-phosphate.
- enzymes: uridylyl transferases
1. Subsequent reaction (mediated by
glycosyl transferases)
2. Transfer of the sugar from uridine
diphosphate to a suitable acceptor
(aglycone) -> glycoside

Classification of the glycoside-containing drugs

follows this scheme:
1. Cardioactive group
2. Anthraquinone group
3. Saponin group

4. Cyanophore group
5. Isothiocyanate group
6. Flavonol group
7. Alcohol group
8. Aldehyde group
9. Lactone group
10. Phenol group
11. tannins
ANTHRAQUINONE GLYCOSIDES
Chrysarobin (too irritating)
Hydrolysis -> algycones (di-,tri- or tetrahydroxyanthraquinones
- example:
- frangulin
- hydrolyzes -> emodin and rhamnose
Anthraquinone and related glycosides are
stimulant cathartics
- by increasing the tone of the smooth muscle in
the wall of the large intestine
Glycosides of anthranols and anthrones elicit a
more drastic action
- can cause discomforting griping action
BIOSYNTHESIS OF ANTHRAQUINONE
GLYCOSIDES
Feedings of labeled acetate to Penicillium
islandicum (produces several anthraquinone
derivatives)
Transglycosylation reaction creates a
glycoside (occurs at a late stage)
CASCARA SAGRADA
Aka Rhamnus purshiana
Rhamnus pushianus (rhamnaceae)
Should be aged for at least one yr
Glycosides are converted to monomeric
oxidized glycosides (which exhibit a milder
cathartic activity
Two types of anthracene compounds:
- normal O- glycosides (10%-20%)
- aloinlike C glycosides (80%-90%)
Two of the c- glycosides:
- barbaloin
- deoxybarbaloin (chrysaloin)
Four additional compounds:
- cascarosides A,B,C, and D
Cascarosides A and B based on optical
isomers of barbaloin
Cascarosides C and D optical isomers of
chrysaloin
Barbaloin and chrysaloin are both O- and Cglycosides
Yields not less than 7% of total
hydrocyanthracene derivatives
Hydrolysis -> rhamnose and glucose (1:1)

USE: cathartic
- PRINCIPAL USE: correction of habitual
constipation ( not only acts as laxative but
restores natural tone to the colon)
Bitter taste and the activity are reduced by
treating it with alkaline earths/ magnesium
oxide
USUAL DOSE :
- cascara sagrada fluid extract (bitter cascara) 1
mL
- aromatic cascara sagrada (sweet cascara) 5Ml
- cascara sagrada extract 300 mg

FRANGULA / BUCKTHORN BARK

Dried bark
Rhamnus frangula
Composition and activity correspond to those of
cascara sagrada
Cathartic
Other spp contain anthraquinons glycosides
Movicol = frangula +karaya
ALOE
-

Aloe or aloes
Dried latex (juice) of the leaves
Aloe barbadensis
- Commerce: curacao aloe
A. ferox, A. Africana, A. spicata
- commerce: cape aloe
Yields not less than 50% of water soluble
extractive
Curacao aloe
- often called Barbados aloe
Occurs in the market: opaque; reddish black to
brownish black to dark brown in color
Principle constituent: barbaloin
Active constituents of aloe may vary
Curacao aloe is superior to cape aloe
- cause it contains two and one half times as
much aloe emodin
- also contains an appreciable amount of free
and combined chrysophanic acid not present in
the other types
USE: pharmaceutic aid, cathartic (acts chiefly
on the large intestine)

ALOE VERA GEL

Fresh mucilaginous gel
Contained in the parenchymatous tissue in the
center of the leaves of Aloe barbadensis
Treatment of burns, abrasions and other skin
irritations

Recommended in treating third degree xray

burns and more recently has been advocated for
its moisturizing and emollient effects
RHUBARB
Rheum, rhubarb or chinese rhubarb
Dried rhizome and root
Rheum officinale ; R. palmatum; Rheum spp.
(except R. rhaponticum common garden
rhubarb)
Fam: Polygonaceae
INDIAN RHUBARB/ HIMALAYAN RHUBARB
Dried rhizome and root
R. emodi, R. spp.
Principle contistuents: rhein anthrones
Cathartic
SENNA
senna leaves
dried leaflet
Cassia acutifolia
-commerce: Alexandria senna
C. angustifolia
- commerce: tinnevelly senna
Fam leguminosae
ALEXANDRIA SENNA
- cutting off the tops, drying them, stems and
pods are separated by sieves, sediments are then
tossed (leaves are at the top, stalk sink to the
bottom)
TINNEVELLY SENNA
- gathered by hand and dried
Graded according to:
- size of the leaf
- color of the leaflets
Blue green leaves best
Yellowish leaves poorest
Principal active constituents: dimeric glycosides
- composed of aloe emodin and/or rhein
Sennosides A and B greatest concentration
- algycones: rhein dianthrone (sennidin A and B)
Sennosides C and D minor constituents
- dimeric algycones composed of 1 molecule of
rhein and 1 molecule of aloe-emodin.
USE: cathartic
USUAL DOSE: 2g
CHRYSAROBIN
Mixture of neutral principles
Obtained from goa powder
From the lysogenous cavities in the wood
Andira araroba
Fam: leguminosae

Hot benzene is used to extract chrysarobin (5070%)

Contains approx.
- 30%-40% chrysophenolanthrone/
chrysophenolanthranol
- 20% emodinanthrone- monomethyl ether
- 30% of dehydro-emodinanthrone-monomethyl
ether
USE: keratolytic agent, treatment of psoriasis,
trichophytosis and chronic eczema
Very irritating to mucous membranes
Should not be used on the face or scalp
ANTHRALIN (synthetic anthracenetriol) has
replaced the use of chrysarobin

DANTHRON
Danthron and chrysazin
1,8-dihydroxyanthraquinone
Insoluble in water
Soluble in alcohol, ether, benzene, and other
solvents
Difficult to isolate in a pure state
USE: cathartic; intermediate in the manufacture
of anthralin and of alizarin and indanthrene
dyestuffs
USUAL DOSE: 75-150 mg
SAPONIN GLYCOSIDES
Form colloidal solutions in water
-foams upon shaking
Irritating to the mucous membrane
Destroy red blood corpuscles by hemolysis
Toxic (esp to cold blooded animals)
Present in fish poisons (many)
Hydrolysis -> sapogenin (algycone)
Can form readily crystallizable compounds
upon acetylation
- can be used to purify sapogenins
Sapatoxins poisonous saponins
Example:
- Chlorogalum pomeridianum (California soap
plant) -> (yields amolonin)
- source of saponin that is used for the industry
Determination of the initial desirability of any
given steroid compound as a cortisone precursor
is based on:
- hydroxyl groups (in the 3- and 11- positions)
or
- the ability to be converted readily to this
structure
Most outstanding plant steroids:
- diosgenin and botogenin (genus dioscorea)
- Hecogenin,, manogenin and gitogenin (agave

spp.)
- sarsasapogenin and smilagenin (genus smilax)
- sitosterol (from crude vegetable oils)
Stophanthus in the apocynaceae was formerly
thought to be the most promising of the
dicotyledons

BIOSYNTHESIS OF SAPONIN GLYCOSIDES

2 types (based on chemical structure)
- neutral saponins : derivatives of steroids with
spiroketal side chains
- acid saponins possess triterpenoid structures
Main pathway leading to both types of
sapogenins is similar and involves the head to
tail coupling of acetate units
GLYCYRRHIZA
Aka licorice root
Dried rhizome and roots
Glycyrrhiza glabra
- commerce: Spanish licorice
G. glabra (var. glandulifera)
- commerce: Russian licorice
Contains glycyrrhizin (glycyrrhizic acid)
- 50x as sweet as sugar
Upon hydrolysis
- loses its sweet taste
- converted to the aglycone glycyrrhetic acid
plus 2 molecules of glucuronic acid
Glycyrrhetic acid pentacyclic tritrepene
derivative of the -amyrin type.
Other constituents:
- flavonoid glycosides ( liquiritin, isoliquiritin,
liquiritoside, isoliquiritoside, rhamnoliquiritin,
and rhamnoisoliquiritin)
- coumarin derivates ( herniarin and
umbelliferone)
- asparagine
- 22, 23-dihydrostigmasterol
- glucose
- mannitol
- 20% starch
USE: demulcent, expectorant ; flavoring agent
(mask the bitter taste of aloe, ammonium
chloride, quinine and others); facilitate
absorption of poorly absorbed drugs (due the
surfactant property; such as anthraquinone
glycosides)
When it is added to
- beer = increases the foaminess
- rootbeer, stout, and porter = imparts a bitter
taste
Glycyrrhetic acid uses:
- anti inflammatory
- treatment of peptic ulcer and of addisons

disease (chronic adrenocortical insufficiency)

- ingredient on Lydia E. pinkham tablets and
vegetable compound liquid for menstrual
problems
Increases fluid and sodium retention and
promotes potassium depletion
PURE GLYCYRRHIZA EXTRACT OR PURE
LICORICE ROOT EXTRACT
- ingredient in aromatic cascara sagrada
fluidextract
GLYCYRRHIZA FLUIDEXTRACT
- pharmaceutic aid

DIOSCOREA
Yam
Mexican yams: rich sources of the principles
used as cortisone precursors
Botogenin and diosgenin
-from Dioscorea spiculiflora (cultivated
species)
- root
Note: the steroid nucleus of botogenin was
altered by transferring an oxygen atom from the
12- to the 11- position of the polycyclic
molecule before it could be utilized as an
intermediate in the production of cortisone
Diosgenin
-obtained upon hydrolysis of dioscin
-major precursor of glucocorticosteroids
MEXICAN YAM
-D. floribunda
- best source of steroids
CYANOPHORE GLYCOSIDES
Commonly found in rosaceous plants
Sometimes designated as cyanogenic glycosides
Most widely distributed of these is amygladin
(another hydrolytic product is benzaldehyde)
Common cyanophore glycosides are derivatives
of madelinitrile
Seeds
Amygdalin and prunasin yield Dmandelonitrile
Sambunigrin (from Sambucus nigra) liberates L
mandelonitrile
Amygdalin is hydrolyzed -> glucose + glucose
- true glucoside rather than a maltoside
Hydrolysis takes place in 3 steps
1. Molecule is hydrolyzed to liberate 1 molecule
of glucose and 1 molecule of mandelonitrile
glucoside
2. Second molecule of glucose is liberated with
the formation of mandelonitrile
3. Mandelonitrile then breaks down with the

formation of benzaldehyde and hydrocyanic

acid
Emulsin (from almond kernels) consists of 2
enzymes:
- amygdalase (causes the first step)
- prunase (causes the second step)
*it is said that the emulsion consists of 4
enzymes
USE: flavoring agents, anticancer claims (not
recognized) , possibility for control of sickle cell
anemia

WILD CHERRY
Aka. Prunus virginiana, wild black cherry tree
Dried stem bark
Prunus serotina
Fam. Rosaceae
Contains a cyanogenic glycoside, prunasin (Dmandelonitrile glucoside)
- formed by the partial hydrolysis of amygdalin
Other constituents:
- hydrolytic enzyme, prunase, p coumaric
acid, trimethyl gallic acid, starch, and traces of a
volatile oil
Resin yields
- 0.23 0.32% in inner bark
- 0.03% in trunk bark
Exposure is such that the chloroplastids are
abundant in the cells of the bark = Dmandelonitrile glucoside is higher
Exposure is such that the cells dont take an
active part in photosynthesis glucoside is
lower
USE: flavored vehicle (esp in cough remedies);
sedative expectorant
ISOTHIOCYANATE GLYCOSIDES
aka glucosinolates
- represent a group of bound poisons like the
cyanogenic glycosides
Aglycones = isothiocyanates
From cruciferous plants
May be aromatic or aliphatic
Principal among these glycosides are
- sinigrin (from black mustard)
- hydrolyze to allyl isothiocyanate
- sinalbin (from white mustard)
- hydrolyze to acrinyl isothiocyanate
- gluconapin (from rape seed)
Examples: horse radish, turnips, mustard,
broccoli, cabbage
S atom is conjugated with glucose as the S
glycoside

Hydrolyzed -> mustard oils

- enzyme: myrosin
USE: feeding deterrent (insects) ;
anticarcinogenic property
MUSTARD

BLACK MUSTARD
-

Sinapis nigra/ brown mustard

Dried ripe seed
Brassica nigra, B. juncea
Fam. Cruciferae
USE: condiment; local irritant, emetic,
rubefacient, vesicant
Contains:
- fixed oil (30%-35%)
Principal constituent: sinigrin (potassium
myronate)
- usually accompanied by the enzyme myrosin
Allyl isothiocyanate is volatile
- commonly called volatile mustard oil

WHITE MUSTARD/ SINAPIS ALBA

dried, ripe seeds
Brassica alba, Hooker filis
Fam. Cruciferae
Commercially important as black mustard
Contains:
- myrosin (enzyme)
- sinalbin (glucoside
Hydrolysis -> acrinyl isothiocyanate
- less volatile than allyl isothiocyanate
- contains 20 to 25% of fixed oil
GARLIC
USE: antihyperlipidemic; enhances blood
fibrinolytic and inhibits platelets aggregation
Allium sativum (liliaceae)
Allin (inactive) + HOH -> allicin -> E ajoene +
Z ajoene
- Z ajoene more bioactive
- Both has antithrombic property (but Z is more
active)
Allicin antibac, responsible for odor and
flavor
FLAVONOL GLYCOSIDES
Flavonoids = flavonol glycosides and their
aglycones
Best known flavonoid constituents:
- rutin, quercitrin, and the citrus bioflavonoids
(hesperidin, hesperetin, diosmin and naringen)
RUTIN AND HESPERIDIN
- aka vit. P / permeability factors

- USE: treatment of various conditions

characterized by capillary bleeding and
increased capillary fragility
CITRUS BIOFLAVONOIDS
- USE: treating symptoms of the common
cold
- NEVER USE WITH HOT WATER
They are included in some preparations as
dietary supplements
Yellow pigments in higher plants

ALCOHOL GLYCOSIDES
SALICIN
Salix spp. , populous spp.
Most willow and poplar barks yield salicin
Principal sources: Salix purpurea, S. fragilis
Populin (benzoyl salicin) is associated with the
salicin in the barks of salicaceae
Hydrolyzed -> D-glucose and saligenin (salicyl
alcohol)
- by emulsion
USE: antirheumatic; closely resembles that of
salicylic acid
DOSE: 1g
ALDEHYDE GLYCOSIDES
Vanilla is a drug that has an aldehydic aglycone
as its chief constituent
Vanillin aglycone developed
- methylprotocatechuic aldehyde
VANILLA (develops during the curing process)
Vanilla bean
Full grown, unripe fruit
Vanilla planifolia
- commerce: mexican/ bourbon vanilla
V. tehitensis
- commerce: Tahiti vanilla
Fam. Orchidaceae
Green vanilla contains two glycosides:
- GLUCOVANILLIN (avenein)
- GLUCOVANILLIC ALCOHOL
Glucovanillin
- hydrolyzed (during the curing process) ->
glucose + vanillin
Glucovanillic alcohol
- hydrolyzed -> glucose + vanillic alcohol
- oxidized -> vanillic aldehyde (vanillin)
USE: principal flavoring constituent (flavoring
agent); pharmaceutic aid; source of vanillin
Contains about 10% of sugar, 10% of fixed oil
and calcium oxalate

COMMERCIAL VARIETIES:
MEXICAN/ VERA CRUZ VANILLA
Best grade
Pods are usually 30-35 cm
BOURBON VANILLA
Resembles the Mexican variety
Two thirds as long
Blacker in color
Covered with a sublimate of needle shaped
vanillin crystals
Possesses a coumarinlike odor
TAHITI VANILLA
Reddish brown in color
As long as the Mexican variety
Sharply attenuated
Twisted in the lower portion
Unpleasant odor
Less suitable for flavoring
VANILLA SPLITS AND CUTS
More mature fruits in which dehiscence has
taken place
VANILLIN
4-hydroxy-3-methoxybenzaldehyde/
methylprotocatechuic aldehyde
May be natural or semi synthetic
or from other sources:
- coniferin (glycoside preset in the cambium sap
of pine trees)
- eugenol (phenol present in clove oil)
- lignin (by product of the pulp industry)
Most of the vanillin in commerce is made from
lignin
Slightly soluble in water and glycerin
Freely soluble in alcohol, chloroform and ether
USE: flavoring agent
Note:
- lignin is found in the rings
- responsible for the color of the tree
ETHYL VANILLIN
Synthetic analog of vanillin
Flavoring agent
LACTONE GLYCOSIDES
Glycosides containing coumarin are rare
None of the hydroxycoumarin glycosides is of
particular medicinal importance
Skimming (Japanese star anise)
Aesculin (horse chestnut tree)

Daphnin (ash bark)

Scopolin (belladona)
Coumarin
Tonka beans
Dipteryx odorata
D. oppositifolia
Viburnum prunifolium (blackhaw)
- antispasmodic activity
V. opulus (true cramp bark)
- fam. Caprifoliaceae
- attributed to scopolefin (6-methoxy-7hydroxy-coumarin)
Others have antispasmodic activity
Once was used as uterine sedatives
Lactone containing natural products:
- cantharidin
- methoxsalen
- santonin
- from Artemisia cina, A. maritima, Artemisia
spp.
- fam. Compositae
- formerly used as an anthelmintic
- discontinued because of potential toxicity

COUMARIN
Lactone of o-hydroxycinnamic acid
Soluble in alcohol
Can be synthesized readily
Occurrence in tonka beans (1%-3%)
- from sweet vernal grass (Anthoxanthum
odoratum) -> fam. Gramineae
- sweet colver (Melilotus albus)
- M. officinalis (fam. Leguminosae)
- sweet scented bed straw (Galium triflorum) ->
fam. Rubiaceae
- red clover (Trifolium pretense) -> fam.
Leguminosae
Formerly flavoring agents
Banned
USE: Antispasmodic, flavoring agent,
anticoagulant (dicumarol/ bishydroxycoumarin),
uterine sedatives, dermatologic purposes
(cantharidin & methoxsalen), anthelmintic
(santonin)
BISHYDROXYCOUMARIN/ DICUMAROL
Related to coumarin
Melilotus officinalis (leguminosae)
Now prepared synthetically
USE: anticoagulant (include warfarin salts)
USUAL DOSE: 200-300 mg initially then 25
-200 mg once a day
CANTHARIDES

Aka. Spanish flies, Russian flies, blistering flies

Dried whole insect
Cantharis vesicatoria (meloidae)
Dried not higher than 40 degrees

Chloroform/ carbon tetrachloride

- added occasionally to preserve the drug from
attack by other insects

Chief constituents
- cantharidin (0.6% - 10%)
- vesicating principle
- lactone/ anhydride or cantharidic acid
- 12% of a fat is associated with the cantharidin

USE: irritant, vesicant, rubefacient

Excreted by the kidney
Irritates the urinary tract
- can result in priapism