PH-PHR 223 Pharmacognosy and Plant Chemistry LEC midterms

GLYCOSIDES AND TANNINS <many tannins are glycosides because of the

LEARNING OBJECTIVES sugar component, some tannins do not have
At the end of this session, the students must be able sugar>
to:
- Identify and familiarize plant glycosides and their FUNCTIONS
structure-activity relationships and plant sources - Conversion of toxic materials to non or less toxic
- Identify extraction methods of plant glycosides substances
and chemical reactions - Transfer water insoluble substances by using
- Highlight therapeutic uses, mechanism of action, monosaccharide <into soluble ones>
possible adverse effects, and toxicity of natural - Source of energy (sugar reservoir, carbohydrates)
plant glycosides as medicine - Storage of harmful products such as phenol
- Define tannins - Regulation of certain plant functions (growth)
- Differentiate the types of tannins - Attractant for pollination because of colors
- Identify tannins and their structure-activity - Defense system against pathogens and
relationships and plant sources herbivores
- Identify extraction methods of tannins and
chemical tests for identification BIOSYNTHESIS
- Highlight therapeutic uses, mechanism of action, - Glycone – from photosynthesis; inactive part -
possible adverse effects, and toxicity of tannins - Actual glycoside - formation of UDP-sugar
as medicine then condensation with the aglycone
- Though most glycones contribute no activity,
PART 1: INTRODUCTION AND BIOSYNTHESIS they can play a role in polarity and thus
GENERAL STRUCTURE solubility/absorption potential ; e.g. in
antibiotics to increase solubility
- Aglycones – too different to be generalized;
active part (imparts the physiological effect)
- Two important pathways include the
mevalonate pathway and shikimic acid
- Glycosides are inactive sugars (glycone) bonded pathway
to a non-sugar active portion (aglycone/genin) - Tannins – also from the shikimic acid pathway
- Glyco - sugar/carbohydrate part
- Usually an ether (R-O-R’) + H2O <95% occurence, UTP + sugar -> UDP(carries sugar, facilitates process
there are special cases with C-glycosides> of combining glycone and aglycone) - sugar +
- Other bonds such as R-C-R’ (C-glycosides), R-N- acceptor (glycoside) *see connection of the two
R’ (N-glycosides) and R-S-R’ (S-glycosides) are parts slide)
possible REVIEW: Mevalonate (MVA) Pathway
- sugar is always cyclic form (hayworth projection)
- Both α and b glycosides are possible; only b form
occurs in plants
- Hydrolysable by mineral acids or enzymes such
as myrosin or emulsin (only target the beta forms
of glycosides; from plants (b))
- Alkalines/bases cannot hydrolyze glycosidic
bonds
- Tannins can be considered as special
polyphenolic glycosides and are discussed later

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PH-PHR 223 Pharmacognosy and Plant Chemistry LEC midterms
- that pathway that gives rise to steroids SHIKIMIC ACID PATHWAY
- terpenes/isoprenoids - super family of
compounds - made of pieces of a molecule
called isoprene (5C)
- Isoprene - does not exist in real life?
(imaginary molecule) - real life equivalent :
IPP 5C (Isopentanyl pryrophosphate) (think
in multiples of 5 (+5 ng +5)
- Mevalonate pathway - terpenoid pathway
1. Acetly CoA (3)
2. HMG-CoA
3. MVA - Mevalonate
4. IPP <also isoprene>
5. DMAPP (5C) isomer
6. Geranyl pyrophosphate (10C)
7. Farsenyl pyrophosphate (15C)
8. 15x2 (20) Squalene -> steroids (part of the many
terpenes) -> cholesterol
9. + IPP = C20PP(Diterpene) -> carotenoids (C40)

- mono - 10, di - 20, tri - 30, sesqui -15

- 10C x (1isoprene/5C)
- Phytol Gibberelins (chlorophyl)
- Cartenoids (beta carotine - vit A)
- Gutta - rubber
- Fragrant oils - monoterpenes
- not the only terpenoid pathway to build IPP

Alternative to mevalonate: The MEP/DOXP Pathway

1. PEP +E4P //fast forward//
2. Shikimic Acid
3. Chorismic acid <Chorismate> can go to another
pathe
4. Prephenic Acid / Anthranilic Acid -> Amino
acids
1. Phenyl pyruvic (Phe) / p-Hydrocyphenyl-
pyruvic acid (Tyr) -> Phenylpropanoids
2. Serine (Trp)
1. Pyruvate 1. Amino Acids + Benzene = Aromatic A.A.
2. G3P
3. DOXP - Gives rise to aromatic amino acids
4. MEP <independent of the Mevalonate - Present in plants but NOT animals
Pathway> for those who have plastids (plants) - humans do not have the enzymes for this
5. IPP pathway
** MEV -> MVA - The prephenic acid branch can also give rise to
the phenylpropanoids (shortcut: C6 -C3 ’s)
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PH-PHR 223 Pharmacognosy and Plant Chemistry LEC midterms
- Many glycosides and volatile oils are classified as - Lignans are single molecules created by union of
phenylpropanoids two phenylpropanoid molecules (see above)
- very wide scope of products from this pathway - Lignin - polymeric substance that assists cellulose
- All of them have phenyl groups (Aromatic) in strengthening cell walls
(glycoside + benzene = from the shikimic acid - Important lignans include silymarin
pathway) derivatives (see flavonoid glycosides) and
- if may steroids -> from mevalonate pathway podophyllotoxin (will be revisited in resins)
- Lignin sample structure:

PART 2: GLYCOSIDES

2A) GLYCOSIDES RELATED TO THE SHIKIMIC ACID

PATHWAY
- Anthraquinones
- Phenolic

LIGNANS

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PH-PHR 223 Pharmacognosy and Plant Chemistry LEC midterms
- Flavonoids - Other anthraquinones come from the polyketide
- Alcohol (salicylic acid) pathway, which utilizes poly β-ketomethylene
- Aldehyde (vanillin) acid is assumed to have formed from 8 acetate
- Lactone (from coumaric acid) units which on being subjected to intramolecular
- Lignans (will be revisited in resins) condensation

A) ANTHRAQUINONE GLYCOSIDES *boxed = C-glycoside

- Aglycones are oxidized forms of anthracene
(three benzene rings together) - Orange-red colored compounds
- Can be classified as: - Soluble in dilute alcohol and boiling/hot water
- anthraquinones (2 =O) - Give a red, violet, or green color with a base (ex.
- oxanthrones (1 -OH and 1 =O) - Cascara NH3 /NaOH)
- anthranols (1 -OH) - Andira araroba - Basis of Borntrager’s test
- anthrones (1 =O) - Characteristic of their cathartic action, except for
- dianthrones (two anthrones bonded) - chrysarobin, which is too irritating to the GIT
Cassia, Rheum, Rhamnus
- Being aromatic, it is expected they come from BORNTRAGER’S TEST
shikimic acid (chorismate branch) - Involves extraction using organic solvent followed
by addition of base
- (+) red color on the lower alkaline layer
- (-) indicates a very stable form of anthraquinone
esp. the reduced types of anthranol (the sample
must be hydrolyzed and oxidized first)
- *pumapalpak minsan

MODIFIED BORNTRAGER’S TEST:

- Uses additional ferric chloride/peroxide to force
oxidative hydrolysis
- (+) pink or red color in the alkaline layer
- indicates the presence of a very stable type of
anthraquinone

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PH-PHR 223 Pharmacognosy and Plant Chemistry LEC midterms
EXAMPLES:
1) SACRED BARK
- Synonyms: Cascara sagrada
- Scientific Name: Rhamnus purshianus
- Family: Rhamnaceae
- Constituents: Barbaloin (Cascarosides A and B),
chrysaloin(Cascarosides C and D)
- Uses:
- emodin = anthraquinone
- Cathartic for habitual constipation restores
natural tone of the colon)
4) RHUBARB
- Casanthranol is purified mixture of the
- Scientific Name: Rheum officinale, R. palmatum,
anthranol glycosides, and is combined with
R. raponticum
surfactants or hydrocolloids ; for products
- Family: Polygonaceae
which need solubilization (suspensions/
- Constituents: Rhein anthrones (at 2.2%),
emulsions)
glucorhein, glucogallic acid
- Should be aged for at least 1 year prior to
- Rhanponticin - adulterant from rhapontic
use
- To reduce its bitter taste, cure with MgO or rhubarb – blue fluorescence <should not be
present = low quality>
alkaline earths ; while aging
- Types:
- High-grade (Chinghai, Shensi-type)
2) FRANGULA
- Medium grade (Canton-type)
- Synonyms: Alder buckthorn
- Scientific Name: Dried bark of Rhamnus frangula - Third grade Use: For jaundice, kidney stones
(only claims) ; mostly for cooking
- Family: Rhamnaceae
- Constituents: Frangulin, glucofrangulin
5) SENNAS/ SLIMMING TEA
- Use: Cathartic
- Source: Dried leaflets of
- Note: “Movicol” = frangula + karaya
- Not commonly used in the local setting - Cassia angustifolia (Tinnevelly senna)
- Cassia acutifolia (Alexandria senna)
- Family: Fabaceae
3) ALOE
- Determination:
- Synonyms: Sabila Scientific
- Alexandria: pink w/ MgOAc in daylight,
- Name: Dried latex leaves of
- Aloe barbadensis (Curacao aloe) green-orange in filtered uv
- Tinnevelly: orange w/MgOAc in daylight,
- Aloe ferox/ Aloe spicata (Cape aloe)
yellow-green in filtered uv
- Aloe perryi (Zanzibar/Socotrine aloe)
- Constituents: Sennosides A and B (major),
- Family: Liliaceae
sennosides C and D (minor)
- Constituents: Barbaloin, emodin, aloe emodin
- Use: Very potent cathartic (more so than cascara
(anthraquinones)
sagrada)
- Use: Cathartic, used for compound benzoin
- Cultivated on wet lands resembling rice
tincture
paddies; as successor to rice
- Aloe vera Gel: treatment of burns, abrasions,
- Adulterated with Argel leaves
skin irritations, purgative, alopecia
- Stabilized aloe is used for lotion or yogurt (Solenostemma arghel)
- Blue-green leaves are the best quality, while
production
yellow ones are the poorest quality

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PH-PHR 223 Pharmacognosy and Plant Chemistry LEC midterms
6) GOA POWDER - Carminic acid
- Scientific Name: Andira araroba - Colorant
- Family: Fabaceae
- Constituents: Chrysarobin (anthranol-type) B) PHENOL GLYCOSIDES
- Use: Keratolytic agent, for psoriasis, - Aglycone is a phenolic group
trichophytosis, eczema (derma ; creams and - Detected by Millon’s Test
ointments) - (+) peach/salmon/pink-
- Notes: colored Hg complex of
- Chrysarobin is extracted by hot benzene nitrophenyl derivative
- Chrysarobin is the only anthraquinone - (used to test for tyrosine)
glycoside too irritating for oral use - NOTE: Most tannins (phenolic compounds) and
- Anthralin has replaced the use of flavonoids are also phenol glycosides by
chrysarobin technicality (their structures are intrinsically
phenolic too)
7) ST. JOHN’S WORT (SJW) - Being aromatic, it is expected they come from
- Scientific Name: Hypericum perforatum the Shikimic acid pathway (chorismate branch)
- Family: Hypericaceae
- Constituents: Hyperforin, hypericin
- Hyperforin is a prenylated ring –acts as
reuptake inhibitor -> increase
neurotransmitters
- Was once dubbed as “Nature’s Prozac”
- [What is Prozac?]
- Claims to treat depression (serotonin
reuptake inhibitor)
- SJW is a well-known enzyme inducer
- Enzyme inducers increase drug metabolism
- hydroquinone (from pHBA ; final prdouct) - only
and can potentially lower drug DoA and/or
aglycone of our phenol glycosides. HO-ring-OH
efficacy
1) BEARBERRY
- Hyperforin is a well-known natural product that - Synonyms: Rockberry
induces CYP enzymes
- Scientific Name: Arctostaphylos uva-ursi
- treated as a drug rather than just food or - Family: Ericaceae
supplement
- Constituents: Arbutin, ericolin
- Hydrolysis of arbutin yields hydroquinone
- Use: Diuretic (tickles the urinary tract), astringent
and antiseptic
- Arbutin has some tyrosinase-inhibiting
(tyrosinase produces melanin) effect
- Skin-lightening potential
8) ANTHRAQUINONES AS PIGMENTS - phenols are usually astringent <tumutusok/
Danthron (Chrysazin/ 1,8-dihydroxyanthraquinone)
nagsasara ng pores ; usually found in toners>
- Cathartic
- For production of anthralin and indanthrene
dyestuffs
Cochineal
- Dried female insect of Dactylopius coccus

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PH-PHR 223 Pharmacognosy and Plant Chemistry LEC midterms
C) ALCOHOL GLYCOSIDES

- Aglycone is a hydrocarbon bearing an alcohol

moiety ROH
- Dominated by the salicylates
- saligenin (found in nature) -> salicylic acid (not
naturally found in nature)
- NOTE: Salicylates are alcohols AND phenols at the
same time – some books may classify them under
2) POPLAR
phenols ; in quiz, saligenin is AN ALCOHOL not a
- Scientific Name: Populus tremuloides
PHENOL
- Family: Salicaceae
- Detected by Ester Formation (ethanol)
- Constituents: Populin (benzoylsalicin)
- C2H5OH + CH3COOH ----> CH3COOC2H5
- Use: Quinine substitute
(ethyl acetate ; plastic balloon order)
- Expectorant, antipyretic, analgesic
- Test for salicylates: FeCl3 (+) violet (usually used
- Common ingredient of herbal cough
for ASA <aspirin>
mixtures

OTHER ALCOHOL GLYCOSIDES

3) BLACK HAW (bark) (Viburnum prunifolium,
Caprifoliaceae)
- Has 0.2% salicin, isovaleric acid
- Dysmenorrhea, bleeding, asthma
4) HOPS (dried strobiles) (Humulus lupulus,
Cannabinaceae)
- Lupulin, reddish brown powder with bitter
aromatic taste (bitterness in beer)
- from chorismate to SA - Phloroglucinol derivatives: humulone (α –
- saligenin = Salicyl Alcohol <present in nature> acids), lupulone (β-acids)
EXAMPLES:
- Xanthohumol – cytotoxic effects on CA cells
5) KAMALA (trichomes/ glands) (Mallotus
1) WILLOW
- Scientific Name: Salix purpurea and S. fragilis philippinensis, Euphorbiaceae)
- Family: Salicaceae - Dull red brown powder w/o odor or taste
- Constituents: Salicin (also found in poplar) - Rottlerin, isorottlerin – anthelmintic
- Salicin is hydrolyzed to yield salicylalcohol by - Used for tapeworm infestation
emulsin
- Salicylalcohol can be oxidized in the lab to — end March 5 —
yield salicylic acid <alcohols -> (oxidized)
aldehydes -> (oxidized) acids>
- Antirheumatic, anti-inflammatory

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