GLYCOSIDES

Glycosides are compounds that yield one or more sugars among the products of hydrolysis. The most
frequently occurring sugar is beta -D-glucose, although rhamnose, digitoxose, cymarose, and other
sugars are components of glycosides. When the sugar formed is glucose, the substance may be called a
glucoside; however, because other sugars may be developed during the hydrolysis, the term glycoside is
applied.

Chemically, the glycosides are acetals in which the hydroxyl of the sugar is condensed with a hydroxyl
group of the non-sugar component, and the secondary hydroxyl is condensed within the sugar molecule
itself to form an oxide ring. More simply, glycosides may be considered sugar ethers. The non-sugar
component is known as the aglycone; the sugar component is called the glycone. Both alpha and beta
glycosides are possible, depending on the stereo configuration of the glycosidic linkage. However, one
should note that only beta forms occur in plants. It should be noted also that emulsin and most other
natural enzymes hydrolyze only the beta varieties.

FORMATION OF GLYCOSIDES:
CLASSIFICATION OF GLYCOSIDES (ON THE BASIS OF ATTACHMENT OF SUGAR RESIDUES)

Glycosides can be classified based on the attachment of the sugar residue into several categories. Here
are some common classifications:

1. O-Glycosides: In these glycosides, the sugar residue is attached to the oxygen atom of another
functional group, typically an alcohol or phenol. Examples include many natural products like flavonoids
and alkaloids; Most phenolic glycosides Rhein-B-Glycosides (Rhubarb).

2. N-Glycosides: Here, the sugar residue is attached to the nitrogen atom of another functional group,
often an amine. N-glycosides are commonly found in nucleosides, where a sugar molecule is attached to
a nitrogenous base, forming the building blocks of nucleic acids. Eg: nucleoside

3. C-Glycosides: In C-glycosides, the sugar residue is linked directly to a carbon atom of the aglycone (the
non-sugar part of the molecule). These glycosides are relatively rare compared to O- and N-glycosides.
An example is found in certain plant constituents like flavonoids. . Eg- Mangiferin in the roots of
Mangifera indica; Barbaloin in Aloe sp.

Mangiferin (1,3,6,7-Tetrahydroxy-2-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]-9H-xanthen-9-one) is a bioactive

ingredient predominantly isolated from mango tree with potent antoxidant activity and antifactorial pharmacological
effects, including anti-diabetic,anti-tumo, lipometabolism regulating, cardioprotective, anti-hyperuricemic,
neuroprotective, anti-oxidant, anti-inflammatory, anti-pyretic, analgesic, anti-bacterial, anti-viral, and
immunomodulatory effects. Therefore, it possesses several health-endorsing properties and it is promising candidate
for further research and development. Barbaloin have variety of pharmacological activity such as strong
inhibitory effect on histamine release, anti-inflammatory, catharatic, anti-viral, antimicrobial, anticancer,
anti-oxidant activity, and alternative for pharmaceutical or cosmetic applications.
4. S-Glycosides: In S-glycosides, the sugar residue is attached to a sulfur atom. These types of glycosides
are less common and are primarily found in certain natural products, such as some sulfur-containing
secondary metabolites in plants. Eg- Glucosinolate found in Brassica nigra (Sinigrin in mustard oil).

CLASSIFICATION OF GLYCOSIDES (BASED ON THE NATURE OF GENIN

PART): -
When the chemical nature of the aglycone group is used as a basis of systematization, the classification
of the glycosidecontaining 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; and (11) tannins.

1. CARDIOACTIIVE GLYCOSIDES: Some steroids present in nature are characterized by the highly
specific and powerful action that they exert on the cardiac muscle. These steroids occur as glycosides
with sugars attached at the 3-position of the steroid nucleus. Because of their action on the heart
muscle, they are named cardiac glycosides. The steroid aglycones or genins are of 2 types: a cardenolide
or a bufadienolide.

The more prevalent in nature are the cardenolides, which are –C23 steroids that have as a 17-beta side
chain an alpha, beta -unsaturated 5-membered lactone ring. The bufadienolides are C 24 homologs of the
cardenolides and carry a doubly unsaturated 6-membered lactone ring at the 17-position.

An unusual aspect of the chemistry of both cardenolides and bufadienolides is that the C/D ring junction
has the cis-configuration. To obtain optimum cardiac activity, the aglycone should possess an alpha,
beta unsaturated lactone ring that is attached beta at the 17-position of the steroid nucleus and the A/B
and C/D ring junctions should have the cis-configuration. Metabolic reduction of the double bond in the
lactone ring of digoxin to form dihydrodigoxin may explain why certain individuals are refractory to
digoxin therapy.

Oxygen substitution on the steroid nucleus also influences the distribution and metabolism of
glycosides. In general, the more hydroxyl groups on the molecule, the more rapid the onset of action
and the subsequent dissipation from the body.

Digitalis: - Digitalis or foxglove is the dried leaf of Digitalis purpurea.

Digitalis Ianata or Grecian foxglove is the dried leaves of Digitalis lanala, a plant indigenous to southern
and central Europe. It is the source of digoxin and desacetyllanatoside C; however, nearly 70 different
glycosides have been detected in the leaves of P. lanata. The composition of 19 of the most important of
these is listed in Table 7-3. All are derivatives of 5 different aglycones, 3 of which (digituxigeriin,
gitoxigenin, and gitaloxigeriin) also occur in D. purpurea. The other 2 types of glycosides derived from
digoxigenin and diginatigenin occur in D. lunate but not in D. purpurea.

Constituents of Digitalis: The drug contains a large number of glycosides of which the most important
from a medicinal viewpoint are digitoxin, gitoxin, and gitaloxin. The total concentration of these 3
glycosides varies appreciably with the plant source and the conditions of growth. Also, because all are
secondary glycosides derived by hydrolysis of some of the sugars from the primary or parent glycosides
occurring in the leaf, their concentration depends on the manner of treatment of the plant material
following harvesting.

DIGITOXIN: Digitoxin is a cardiotonic glycoside obtained from D. purpurea, D. lanata, and other
suitable species of Digitalis. On hydrolysis, digitoxin yields 1 molecule of digitoxigenin and 3 of
digitoxose. It is a highly potent drug and should be handled with exceptional care. Digitoxin occurs as a
white or pale buff, odorless, microcrystalline powder. It is a bitter substance that is practically insoluble
in water and slightly soluble in alcohol. It is the most lipid-soluble of the cardiac glycosides used in
therapeutics.

Deslanoside: Deslanoside is desacetyllanatoside C, which on hydrolysis yields 1 molecule of digoxigenin,

3 of digitoxose, and I of glucose. Deslanoside occurs as a white, crystalline powder. It is hygroscopic,
absorbing about 7% of moisture when exposed to air, and is highly potent. Deslanoside is frequently
used to attain rapid initial loading by parenteral administration.

ConvaUaria or lily-of-the-valley root is the dried rhizome and roots of Couvallaria majalis Linné (Fam.
Liliaceae). More than 20 cardioactive glycosides have been isolated from this drug. Principal among
these is convallatoxin, a monoglycoside composed of the genin of K-strophanthin (strophanthidin) and
the sugar of G-strophanthin (rhamnose). Other minor glycosides include convallatoxol and convalloside.

Black hellebore or Christmas rose is the dried rhizome and roots of Helleborus niger Linné (Fam.
Ranunculaceae). The chief constituent is hellebrin.
2. Anthraquinone glycosides: A number of glycosides with aglycones related to anthracene are present
in such drugs as Cascara sagrada, Frangula, Aloe, Rhubarb, Senna, and Chrysarobin. With the exception
of Chrysarobin (which is too irritating), these drugs are employed as Cathartics. The glycosides, upon
hydrolysis, yield aglycones that are di-, tri-, or tetrahydroxyanthraquinones or modifications of these
compounds.

The free anthraquirione aglvcones exhibit little therapeutic activity. The sugar residue facilitates
absorption and translocation of the aglycone to the site of action. The anthraquinone and related
glycosides are stimulant cathartics and exert their action 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 than
do the corresponding anthraquinone glycosides, and a preponderance of the former constituents in the
glycosidic mixture can cause discomforting griping action.

BIOSYNTHESIS OF ANTHRAQUINONE GLYCOSIDES. Much of our knowledge of the biosynthesis of

anthraquinones has been obtained from studies of microorganisms. Feedings of labeled acetate to
Penicillium islandicum, a species that produces several anthraquinone derivatives, have revealed that
the distribution of radioactivity in these compounds is consistent with formation via a head-to-tail
condensation of acetate units. A poly- beta-ketomethylene acid intermediate is probably first produced
and then gives rise to the various oxygenated aromatic compounds following intramolecular
condensations. Anthranols and anthrones are likely intermediates in the formation of anthraquinories.
Presumably, the emodin-like anthraquinones are formed in higher plants by a similar pathway. The
transglycosylation reaction, which creates a glycoside, probably occurs at a late stage in the pathway
after the anthraquinone nucleus has been formed.

 CASCARA SAGRADA: Cascara sagfada or rhamnus purshiana is the dried bark of Rhamnus
purshianus. The species epithet was formerly spelled purshiana, and that form is retained in one
of the titles applied to the drug. Two types of anthracene compounds have been reported:
normal O-glycosides (based on emodin), about 10 to 20%, and aloinlike C-glycosides,
representing about 80 to 90% of the total. About a dozen such compounds have been identified.
Two of the C-glycosides are barbaloin and deoxybarbaloin (chrysaloin). Four additional
compounds of this type are designated as cascarosides A, B, C, and D. Cascarosides A and B are
based on optical isomers of barbaloin and cascarosides C and D on optical isomers of chrysaloin.
All 4 of the cascarosides, being primary glycosides of barbaloin and chrysaloin, are actually both
0- and C-glycosides. . Cascara sagrada is the active ingredient in CasEvac® and a number of
generic products.

Casanthranol is a purified mixture of the anthranol glycosides extracted from cascara sagrada. It is
marketed as Lane's Pills®. Casanthranol is also combined with surfactant drugs and/or hydrocolloids;
such formulations include Afko-Lube Lax®, Comfolax PJus®, Constihan ® , Dialose Plus®, Diothron®,
Disanthrol ®, DiosIan Forte®, and PeriColace®.

 Frangula or buckthorn bark is the dried bark of Rhamnus frangula Linné. This plant is a shrub
that grows in Europe and western Asia. The composition and activity of frangula bark
 correspond to those of cascara sagrada, and it finds a comparable use in Europe and the Near
East. Products from the dried, ripe fruits of R. catharticus are also used in these areas for their
cathartic action. Other Rhamnus species contain anthraquinone glycosides but are not
employed in medicine. Movicol® contains frangula and karaya gum.
 Aloe: Aloe or aloes is the dried latex (juice) of the leaves of Aloe barbadensis Miller (A. vera
Linné), known in commerce as Curaçao aloe (Fig. 3-4), or of A. ferox Miller and hybrids of this
species with A. africana Miller and A. spicata Baker, known in commerce as Cape aloe (Fam.
Liliaceae). Aloe yields not less than 50% of water soluble extractive.

Aloe contains a number of anthraquinone glycosides, the principal one of which is barbaloin (aloe-
emodin anthrone C-I0 glucoside). O-Glvcosides of barbaloin with an additional sugar also have been
isolated from certain samples of Cape aloe. These compounds have been designated aloinosides. Free
(nonglycosidal) aloe-emodin and a free and combined anthranol are also present. Chrysophanic acid has
been detected in certain types of the drug. The active constituents of aloe vary qualitatively and
quantitatively according to the species from which the drug is obtained. Analyses have revealed that
Curaçao aloe is superior to Cape aloe because it contains two-and-one-half times as much aloe-emodin.
Curaçao aloe also contains an appreciable amount of free and combined chrysophanic acid not present
in the other types

 Rhubarb: Rhubarb, rheum, or Chinese rhubarb consists of the dried rhizome and root that are
deprived of periderm tissues of Rheum officinale. The principal constituents of medicinal
rhubarbs are rhein anthrones. Rhubarb has been used in cathartic preparations; the Cathartic
action is relatively drastic, and the use of other cathartic substances has largely been adopted.
 Senna: Senna or senna leaves consists of the dried leaflet of Cassia acutifolia Delile, known in
commerce as Alexandria senna, or of C. augustifolia Vahi, known in commerce as Tirtnevelly
senna (Fam. Leguminosae). The principal active constituents of senna are dimeric glycosides
whose aglycones are composed of aloe-emodjn and/or rhein. Those present in greatest
concentration are sennosides A and B, a pair of optical isomers whose aglycones are
rheindianthrone (sennidin A and B). Sennosides C and D are minor constituents having dimeric
aglycones composed of I molecule of rhein and I molecule of aloe-emodin Small quantities of
monomeric glycosides and free anthraquinones are also present. Senna pods also contain
useful, active glycosides; sonic of the primary glycosides in the pods have as many as 10 sugar
molecules attached to a rhein dianthrone nucleus.
 Chrysarobin: Chrysarobin is a mixture of neutral principles obtained from Goa powder. Goa
powder takes its name from the former Portuguese colony on the Malabar Coast of India and is
obtained from lysogenous cavities in the wood of Andira araroba. A representative sample of
chrysarobin contains approximately 30 to 40% of chrysophenolanthrone or
chrysophenolanthranol 20% emodinanthrone-monomethyl ether, and 30% of dehydro-
emodinanthrone - monomethyl ether.

USES. Chrysarohin is a keratolytic agent and has been employed in the treatment of psoriasis,
trichophytosis, and chronic eczema. It is very irritating to mucous membranes and should not he used
on the face or scalp. The variable composition of chrysarobin and the lack of adequate standardization
procedures have created problems in ensuring reproducible therapeutic effects. Anthralin, a synthetic
anthracenetriol, has replaced the use of chrysarobin;

3. SAPONIN GLYCOSIDES: This group of glycosides is widely distributed in the higher plants.
Saponins form colloidal solutions in water that foam upon shaking; they have a bitter, acrid taste, and
drugs containing them are usually sternutatory and otherwise irritating to the mucous membrane. They
destroy red blood corpuscles by hemolysis and are toxic, especially to cold-blooded animals. Many
saponins are used as fish poisons. Upon hydrolysis they yield an aglycone known as a "sapogenin." The
sapogenins form readily crystallizable compounds upon actylization. This process can be used to purify
sapogenins. The more poisonous saponins are often called "sapotoxins." Glycyrrhiza and sarsaparilla are
among the drugs containing saponins. Plants such as the California soap plant, Chlorogalum
pomeridianum, which yields amolonin, are sources of saponins that are used extensively for industrial
purposes.

The determination of the initial desirability of any given steroid compound as a cortisone precursor is
based on whether it has hydroxyl groups in the 3- and 11-positions on the molecule or has the ability to
be converted readily to this structure. It would appear that the most outstanding plant steroids for
cortisone production are: diosgenin and botogen.in from the genus Dioscorea. Hecogenin, manogenin,
and gitogenin from species of Agave. Sarsasapogenin and smilagenin from the genus Smilax.
Sarmentogenin from the genus Strophanthus, Sitosterol from crude vegetable oil.

Biosynthesis of Saponin Glycosides: Saponin glycosides are divided into 2 types based on the chemical
structure of their aglycones (sapogenins). The so-called neutral saponins are derivatives of steroids with
spiroketal side chains; the acid saponins possess triterpenoid structures. Less is known about
triterpenoid biosynthesis than is known about the steroids, but labeled acetate and mevalonate have
been incorporated into such compounds. Therefore, the main pathway leading to both types of
sapogenins is similar and involves the head-to-tail coupling of acetate units. However, a branch occurs,
probably after the formation of the triterpenoid hydrocarbon, squalene, that leads to steroids in one
direction and to cyclic triterpenoids in the other (Fig. 3-7).
  Glycyrrhiza: Glycyrrhiza is the dried rhizome and roots of Glycyrrhiza glabra, known in
commerce as Spanish licorice, or of G. glabra var. glandulifera, known in commerce as Russian
licorice. The fruit in the variety glandulifera has glandlike swellings. Glycyrrhiza is also called
licorice root. Glycyrrhiza contains a saponinhke glycoside, glycyrrhizin (glycyrrhizic acid), which is
50 times as sweet as sugar. Upon hydrolysis, the glycoside loses its sweet taste and is converted
to the aglycone glycyrrhetic acid plus 2 molecules of glucuronic acid. Glycyrrhetic acid is a
pentacyclic triterpene derivative of the beta-aniyrin type. Other constituents include flavonoid
glycosides (liquiritin, isoliquirilin, liquisitoside, isoliquiritoside, rhamnoliquiritin, and
rhamnoisoliquiritin), coumarin derivatives (herniarin and umbelliferone), asparagine, 22,23-
dihydrostigmasterol, glucose, mannitol, and about 20% of starch.
 Dioscorea: Yam is a popular name for several of the edible species of Dioscorea and is
sometimes incorrectly applied to certain varieties of the sweet potato. Various species of
Dioscorea known as Mexican yams represent rich sources of the principles used as cortisone
precursors. Botogenin and diosgenin are obtained from the root of Dioscorea spiculiflora ., a
cultivated species. 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, is
now the major precursor of glucocorticosteroids, which are prepared by processes that involve
microbial transformation. A Mexican yam derived from D. floribunda is considered by the U.S.
Department of Agriculture as the best source of steroids.

4. cyanophore glycosides: Several glycosides yielding hydrocyanic acid as one of the products of
hydrolysis are commonly found in rosaceous plants. They are sometimes designated as cyanogenic
glycosides. Perhaps the most widely distributed of these is amygdalin. (Note that another of the
hydrolytic products is benzaldehyde; thus, amygdalin-containing drugs may also be classified in the
aldehyde glycoside group.)

The common cyanophore glycosides are derivatives of mandelonitrile (benzaldehyde-cyanohydrin). The

group is represented by amygdalin, which is found in large quantities in bitter almonds, in kernels of
apricots, cherries, peaches, plums, and in many other seeds of the Rosaceae, and also by prunasin,
which occurs in Prunus serotina. Both amygdalin and prunasin yield D-mandelonitrile as the aglycone.
Sambunigrin from Sambucus nigra liberates L-mandelonitnle as its aglycone.

When amygdalin is hydrolyzed, it forms 2 molecules of glucose. Although these are usually written as
linked in apparent disaccharide form, one should note that a disaccharide sugar has never been broken
off from the molecule by any known means of hydrolysis. Amygdalin is therefore a true glucoside rather
than a maltoside. The hydrolysis of amygdalin takes place in 3 steps, which briefly are as follows: i. The
molecule is hydrolyzed initially to liberate 1 molecule of glucose and I molecule of mandelonitrile
glucoside.

ii. The second molecule of glucose is liberated with the formation of mandelonitrile.
iii. The mandelonitrile then breaks down with the formation of benzaldehyde and hydrocyanic acid.

The enzyme emulsin, as obtained from almond kernels, consists of a mixture of 2 enzymes: amygdalase,
which causes the first step in the hydrolysis, and prunase, which causes the second step. (It is said that
emulsion consists of at least 4 enzymes.

Preparations from plant materials containing cyanogenic glycosides are widely employed as flavoring
agents. Anticancer claims have also been made for an amygdalin-containing preparation known as
laetrile or vitamin B17, and the possibility for control of sickle cell anemia with cyanogenic glycosides
has been noted.

 Wild Cherry: Wild cherry is the carefully dried stem bark of Prunus serotina (Fam. Rosaceae).
Prunus is the classic name of the plum tree; Serotina means late or backward, referring to the
time of flowering and fruiting of the species: Wild cherry is known as Prunus virginiana and as
wild black cherry tree.
Wild cherry bark contains a cyanogenic glycoside, prunasin (D-mandelonitrile glucoside), a
compound formed by the partial hydrolysis of amygdalin (see Fig. 3-9). Other constituents
include the hydrolytic enzyme, prunase, p-coumaric acid, tri-methyl gallic acid, starch, and
traces of a volatile oil.

5. isothiocyanate glycosides: The seeds of several cruciferous plants contain glycosides, the aglycones of
which are isothiocyanates. These aglycones may be either aliphatic or aromatic derivatives. Principal
among these glycosides are sinigrin from black mustard, sinalbin from white mustard, and gluconapin
from rape seed. When hydrolyzed by the enzyme myrosin, they yield the mustard oils. Although the
fixed oil content of these seeds exceeds the amount of the volatile oil developed on hydrolysis, the
activity is caused by the latter.
  Black mustard : Black mustard, Sinapis nigra, or brown mustard is the dried ripe seed of
varieties of Brassica nigra or of B. juncea or of varieties of these species. Although black mustard
contains fixed oil (30 to 35%), its princIpal constituent is the glycoside, sinigrin (potassium
myronate), which is accompanied (probably in adjacent cells) by the enzyme, myrosin. Upon the
addition of water to the crushed or powdered seeds, the myrosin effects the hydrolysis of the
sinigrin. The allyl isothiocyanate produced is volatile; it is commonly called volatile; it is
commonly called volatile mustard oil.
 White mustard or sinapis alba consists of the dried, ripe seeds of Brassica alba (Fam. Cruciferae).
White mustard is as commercially important a black mustard. The plant resembles that of B.
nigra but is usually considerably shorter, and its siliques are more rounded and tapered. Like
black mustard, it is cultivated in temperate climates all over the world. White mustard contains
the enzyme, myrosin, and a glucoside, sinalbin, which, upon hydrolysis, yield acrinyl
isothiocyanate, a pungent-tasting but almost odorless oil that is much less volatile than allyl
isothiocyanate. It also contains 20 to 25% of fixed oil.

6. flavonol glycosides: The flavonol glycosides and their aglycones are generally termed flavonoids. A
large number of different flavonoids occur in nature, and those yellow pigments are widely distributed
throughout the higher plants. Rutin, quercitrin, and the citrus bioflavonoids (including hersperidin,
hesperetin, diosmin, and naringen.) are among the best-known flavonoid constituents.

Rutin and hesperidin have been called vitamin P or permeability factors. They have been used In the
treatment of various conditions characterized by capillary bleeding and capillary fragility. Claims have
also been advanced for the value if citrus bioflavonoids in treating symptoms of the common cold.
Evidence for the therapeutic efficacy of rutin, citrus bioflavonoids, and related compounds is not
conclusive, and products containing them are no longer marketed for the medicinal purposes in the
United States. They are included in some preparations as dietary supplements.

7. alcohol glycosides:
Salicin: It is a glycoside obtained from several species of Salix and Populus. Most willow and poplar barks
yield salicin, but the principal sources are Salix purpurea and Salix fragilis. The glycoside, populin
(benzoyl salicin), is also associated with the salicin in the barks of the Salicaceae.

Salcin is hydrolyzed into D-glucose and saligenin (salicyl alcohol) by emulsin. Salicin has antirheumatic
properties. Its action closely resembles that of salicyclic acid, and it is probably oxidized to salicyclic acid
in the human system. Recognition of the properties of salicin clarifies many folkloric uses of poplar and
willow barks.

8. aldehyde glycosides: Vanilla is a drug that has an aldehydic aglycone as itd chief component.
Vanillin is the aglycone developed during the curing of vanilla beans. Vanillin is methyiprotocatechuic
aldehyde.

 Vanilla: Vanilla or vanilla bean is the cured, fullgrown, unripe fruit of Vanilla planifolia, often
known in commerce as Mexican or Bourbon vanilla, or of V. tahitensis, known in commerce as
Tahiti vanilla (Fam. Orchidaceae). Green vanilla contains two glycosides, glucovanillin (avenein)
and glucovanillic alcohol. Glucovanillin is hydrolyzed by an enzyme during the curing process
into glucose and vanillin, and glucovanillic alcohol is similarly hydrolyzed into glucose and vanillic
alcohol, which is, in turn, oxidized to vanillic aldehyde (vanillin). Vanillin is the principal flavoring
constituent. Vanilla also contains about 10% of sugar, 10% of fixed oil, and calcium oxalate.
USES. Vanilla, in the form of vanilla tincture, is used as a flavoring agent and as a pharmaceutic
aid. It is a source of vanillin.

Commercial varities:
(i) Mexican or Vera Cruz vanilla is the best grade on the market; the pods frequently attain a
length of 30 to 35 cm. The supply is largely consumed in Mexico and the United States.
(ii) Bourbon vanilla is produced on the island of Reunion and shipped from the Malagasy
Republic. It resembles the Mexican variety but is about two thirds as long, blacker in color,
usually covered with a sublimate of needle-shaped vanillin crystals, and possesses a coumarin-
like odor.
(iii) Tahiti vanilla, grown in Tahiti and Hawaii, is reddish brown in color and about as long as the
Mexican variety but sharply attenuated and twisted in the lower portion. The odor is somewhat
unpleasant, and the variety is less suitable for flavoring.
(iv) Vanilla splits and cuts represent the more a mature fruit in which dehiscence has taken
place. They are cut into short lengths.
(v) Vanillin is 4-hydroxy-3-methoxybenzaldehyde or methylprotocatechuic aldehyde. It may be obtained
from vanilla or prepared synthetically from other sources: (1) coniferin, a glycoside present In the
cambium sap of pine trees; (2) eugenol, a phenol present in clove oil; and (3) lignin, a by-product of the
pulp industry. Most of the vanillin in commerce is made from lignin. Vanillin consists of fine, white to
slightly yellow, needlelike crystals that have an odor and a taste resembling vanilla. It is slightly soluble
in water and glycerin and is freely soluble in alcohol, chloroform, and ether. Vanillin is employed as a
flavoring agent. Ethyl vanillin, a synthetic analog of Vanillin, is also used as a flavoring agent.

9. lactone glycosides: Although coumarin is widely distributed in plants, glycosides containing coumarin
as such are rare. Several glycosides of hydroxylated coumarin derivatives, however, occur in plant
materials; these glycosides include skimmin in Japanese star anise, aesculin in various parts of the horse
chestnut tree, daphniri in mezereum, fraxin in ash bark, scopolin in belladonna, and limettin in citrus
trees. None of the hvdroxycoumarin glycosides is of particular medicinal importance.

 Coumarin: Coumarin is the lacton of o-hydroxycin-namic acid. It occurs as colorless, prismatic

crystals and has a characteristic fragrant odor and a bitter, aromatic, burning taste. It is soluble
in alcohol. Coumarin can be synthesized readily.
Bishydroxycoumarin or dicumarol is a drug related to coumarin. It was obtained originally from
improperly cured leaves and flowering tops of Melilotus officinalis (Fam. Legurninosae), but it is
now prepared synthetically. Dicumarol is anticoagulant.
 Cantharides, Spanish flies, Russian flies, or blistering flies consists of the dried insect, Cantharis
vesicatoria (Fam. Meloidae). Cantharides contains as its chief constituent the vesicting principle,
cantharidin (0.6 to 1.0%), which is the lactone or anhydride of cantharidic acid. In addition,
about 12% of a fat is associated with the cantharidin in the soft body tissues of the insect.
 Psoralens: Psoralens are photosensitizing furocoumarins that occur in a number of plant
families, including the Umbelliferae, where they are a common cause of phototoxicity.
Methoxsalen, 8-methoxypsoralen, or xanthotoxin, a constituent of the cremocarps of Ammi
majus (Fam. Umbellilerae), is used to facilitate repigmentation in idiopathic vitiligo (leukoderma)
and for symptomatic control of severe, disabling psoriasis. Methoxsalen may be applied topically
or taken orally. Therapeutic regimens require cautious patient exposure to ultraviolet radiation
(sunlight); repigmentation therapy usually involves extended periods of time. Risks inherent in
therapy with methoxsalen, including carcinogenesis, cataract development, and actinic
degeneration of the skin, restrict its use to specialists.
10. phenol glycosides: The aglycpne groups of many of the naturallv occurring glycosides are
phenolic in character. Thus, arbutin, found in uva ursi, chimaphila, and other ericaceous drugs, yields
hydroquinone and glucose upon hydrolysis. Hesperidin, which occurs in various citrus fruits and is
included with the flavonol group, may be classified as a phenol glycoside. Phloridzin, found in the
root bark of rosaceous plants, baptisin from baptisia, and iridin from Iris species are additional
examples of phenol glycosides.

11. tannins: Tannins comprise a large group of complex substances that are widely distributed in the
plant kingdom; almost every plant family embodies species that contain tannins. When tannins
occur in appreciable quantities, they are usually localized in specific plant parts, such as leaves,
fruits, barks, or stems.

Chemically, tannins are complex sub- stances; they usually occur as mixtures of polyphenols that are
difficult to separate because they do not crystallize. Some authors prefer to use the term "tannin ex-
tracts" rather than "tannins." Recently, the use of chromatographic methods has enabled research
workers not only to confirm the complicated nature of tannin ex- tracts but also to identify the
simple poly- phenols present in small amounts in such mixtures. Determination of the latter is im-
portant because complex tannins are generally considered to have arisen from simple polyphenols
by polymerization. Many condensed tannins have never been isolated or characterized; thus, their
biogenetic development is not positively known.

Tannins are customarily divided into 2 chemical classes, based on the identity of the phenolic nuclei
involved and on the way they are joined. Members of the first class consist of gallic acid or related
poly hydric compounds esterified with glucose Because such esters are readily hydrolyzer to yield
the phenolic acids and the sugar they are referred to as hydrolyzable tannins.

Nonhydrolyzable or condensed tannin composed the second class. Basically, these tannins contain
only phenolic nuclei but frequently are linked to carbohydrates or proteins. Most such tannins result
from the condensation of 2 or more flavan-3-ols, such as catechin, or of flavan-3,4 -diols, such as
leucocyanidin. When treated with hydrolytic agents, these tannins tend to polymerize, yielding
insoluble, usually red-colored products known as phlobaphenes.

Both classes of tannins are widely distributed in nature. It must be emphasized that, in many
species, both types are present, although one type generally tends to - predominate in any
particular plant part.

TANNIN-CONTAINING PLANT MATERIALS:

 Hamamelis Leaf: Hamamelis leaf or witch hazel leaves is the dried leaf of Hamamelis
virginiana. . Hamameljs leaf contains hamamelitannin and a second tannin that appears to
be derived from gallic acid; a hexose sugar, a volatile oil, a bitter principle, gallic acid, and
calcium oxalate. Hamamelis leaf possesses astringent and hemostatic properties.
USES. Although tannins are not carried over in the distillation process, hamamelis water is
nevertheless widely utilized for its so-called astringent properties. It is incorporated in
hemorrhoidal products, preparations for treating insect bites and stings, and even teething
preparations. The contained volatile oil does confer a pleasant fragrance to such products.

 Nutgall: Nutgall is the excrescence obtained from the young twigs of Quercus infectoria
and allied species of Quercus (Fam. Fagaceae). The galls are obtained principally from
Aleppo in Asiatic Turkey. The principal constituent is tannic acid, which is found to the
extent of 50 to 70%; the drug also contains gallic acid, 2 to 4%; ellagic acid; starch; and resin.
Nutgall, the chief source of tannic acid,is used in the tanning and dyeing industry and,
formerly, in the manufacture of ink. Medicinally, it has astringent properties.
Tannic Acid

Tannic acid, gallotannic acid, or tannin is a tannin usually obtained from nutgall. The powdered galls are
extracted with a mixture of ether, alcohol, and water and the liquid separates into 2 layers. The aqueous
layer contains gallotannin and the ethereal layer contains the free gallic acid present in the gall. After
separation, the solution of gallotannin is evaporated and the tannin is purified in various ways.
COMPOSITION. Tannic acid is not a single homogeneous compound but is a mixture of esters of gallic
acid with glucose, whose exact composition varies according to its source. The tannin from Chinese galls
analyzes entirely as octa- or nonagalloyl-glucose and yields, on hydrolysis, methyl gallate and 1,2,3,4,6-
pentagalloylglucose. Turkish tannin, which is a mixture of hexaor heptagalloylglucoses, hydrolyzes to
form methyl gallate and a mixture of 1,2,3,6-and 1 ,3,4,6-tetragalloylglucose. On milder treatment, both
types of tannic acid yield methyl m-digallate, indicating the presence of a m-digallate group in each.