PHENOL GLYCOSIDES

PHENOL GLYCOSIDES

 Any compound with a hydroxyl group linked directly to a benzene ring is called PHENOL.

PHENOL GLYCOSIDES

 Some phenolic groups are found in the plants in the free state; e.g. thymol, carvacrol, eugenol…

 There are those in the structure of diphenol such as Flavonoids; triphenols such as tannins

thymol quercetin

PHENOL GLYCOSIDES

 There are dimerization derivatives of phenols in phenyl propanoid structure; e.g. lignans

PHENOL GLYCOSIDES

Glycosidic bond between phenolic –OH and sugar is called PHENOL GLYCOSIDE

 Identification and Properties

 They are less soluble in water, polyphenols are slightly more soluble

 They are soluble in alcohol and ether

 Most of them are water-vapor drift  volatile

 They have weak acidic property

 Alkaline phenolates occur with alkaline hydroxides (They dissolve in alkaline hydroxides)  this

PHENOL GLYCOSIDES

 Unlike acids, they don’t dissolve in alkaline carbonates.

Identification with colour reactions:

Free phenols + aqueous ferric chloride (FeCl₃) neutral medium 

blue/green/purple/red colour (But also

hydroxypyridine, some organic acids, enols, oximes may give positive reaction)

PHENOL GLYCOSIDES

 Phenols + amines dinitrozed by nitroso acid (e.g. P-nitranyline)  coloured hydrasoics occur.

 Phenols + aldehydes (e.g. Vaniline-HCl) and 2,6-dibromquinone chlorimide in acidic medium  give colour reactions.

 Phenols + acetic acid and benzoic acid  characteristic esters and meyhyl derivatives occur.

PHENOL GLYCOSIDES

QUANTIFICATION

1) Colorimetric: By using colouring reactions.

2) Chromatographic: Measured upon phenolic aglycones. 3) Titirmetric: Can be applied after extraction with

alkaline hydroxides.

4) Gravimetrically: After phenolics precipated by aquaeous Br, is weighed out and the amount is calculated.

PHENOL GLYCOSIDES

USAGES

1) Some of them are antiseptic 2) Antipyretic and analgesic

3) Some phenolic aglycones are odorous; used as aromatizan or odour improver in pharmaceutical and food industries.

CORTEX SALICIS, Söğüt kabuğu

(WHITE WILLOW)

 The bark of the branches of Salix alba (Salicaceae) (Ak söğüt).

 Grows in damp, temperate and cold regions

 Widespread in Turkey

 Shedding leaves in winter, generally grows near a water source

CORTEX SALICIS, Söğüt kabuğu

(WHITE WILLOW)

 Approximately, 25 Salix species are growing in Turkey Among these species the most common ones are:

 S. alba (ak söğüt – white willow)

 S. babylonica (salkım söğüt - Babylon willow or weeping

willow)

 S. caprea (keçi söğütü – goat willow) S. cinerea (boz söğüt – grey willow)

 S. excelsa (yüksek söğüt - )

 S. fragilis (gevrek söğüt – crack willow)

 S. purpurea (erguvani söğüt – purple willow)

CORTEX SALICIS, Söğüt kabuğu

(WHITE WILLOW)

 Contents

 SALICIN (Phenol glycoside)

 Tannins

 Tonic property regarding tannin content.

 Glycoside  febrifuge, antirheumatic and antineuralgic.

CH₂OH O Gl SALIKOZIT ENZ.HİDR. ASİT HİDR. CH₂OH OH SALİGENOL CH₂ O CH₂ OH OH SALİRETİN + Gl ( Aglikonun dimeri) SALICIN Enz. Hyd. Acid Hyd. SALIGENIN (Salicyl alcohol) SALIRETIN Dimer of aglycone

POPULI GEMMAE (TK),

Karakavak

tomurcuğu, Black poplar

 Flower and leaf buds of Populus nigra (Salicaceae)

collected at the end of winter

 1-3 cm length, conic shaped

 Contents;

 Phenol glycoside  Populin (populoside) (benzoyl salicoside)

CH₂OH O

CH₂OCO O

POPULOZİT (BENZOİL SALİKOZİT)POPULIN (Benzoyl salicin)

CHRYSIN DERIVATIVE (Flavon)

POPULI GEMMAE (TK),

Karakavak

tomurcuğu, Black poplar

 Used in the treatment of hemorrhoid as

ointment

 Populin  painkiller

 Chrysol derivative  increases capillary

resistance

FRUCTUS VANILLAE (TK),

Vanilla fruit, Vanilya meyvesi

 Boiled and then dried immature fruits of Vanilla

planifolia (Orchidaceae).

 Grows naturally and cultured in Meksika, Java, Madagaskar ve Antills.

 15-25 cm, flat, sharp in 2 edges, bright black coloured

 Contents;

 VANILLIN (VANILLAL) ---%1.5-2.5  (Fragrant compound)

 Its glycoside, found in fresh fruit is VANILLOSIDE (Glucovanillin)----β-glucosidase hydrolysis---Vanillin+gl

 VANILLOLOSIDE---Glycoside of Vanillic

alcohol.

FRUCTUS VANILLAE (TK),

Vanilla fruit, Vanilya meyvesi

CHO OGl OCH₃ VANİLOZİT (GLUKOVANİLİN) _CH2OH O OCH₃ OZ VANİLOLOZİT

(VANİLİK ALKOL HET.)

VANILLOSIDE (Glucovanillin)

VANILLOLOSIDE (Vanillic alcohol glycoside)

 Weak choloretic activity

 Digestion stimulant

 Sexual power enhancer effect

 Used for odour correction in the

pharmaceutical and food industries

FRUCTUS VANILLAE (TK),

Vanilla fruit, Vanilya meyvesi

FOLIA UVAE URSI,

Ayı üzümü yaprağı, Bearberry leaf

 Arctostaphylos uva ursi (Ericaceae)

 Growing in mountainous regions

 Europe, Asia, North America

 Doesn’t grow in Turkey

 Contents – Phenol glycosides;

 ARBUTIN (hydroquinone derivative)----%5-10

 METHYL ARBUTIN (methyl hydroquinone derivative)

FOLIA UVAE URSI,

Ayı üzümü yaprağı, Bearberry leaf

Contents – Phenol glycosides;

 ARBUTIN (hydroquinone derivative)----%5-10

 METHYL ARBUTIN (methyl hydroquinone derivative)

O O HİDROKİNON OGl OH ARBUTOZİT OGl OCH₃ METİL ARBUTOZİT HYDROQUINONE ARBUTIN METHYL ARBUTIN

 Arbutin---hydrolysis---hydroquinol  quickly oxidized to hydroquinone

 Gallic tannin

 Flavonoids  Quercetin derivatives

FOLIA UVAE URSI,

 Astringent due to tannin content

 Antiseptic for urinary system; extracts of this plant are used against cystitis, urethritis,

pyelitis

 Antibacterial effect

 Aqueous leaf extract is effective against

Helicobacter pylori due to tannic acid

content

FOLIA UVAE URSI,

FLORES SPIRAEAE ULMARIAE

(MEADOWSWEET)

 Filipendula ulmaria (Spiraea ulmaria)

(Rosaceae) ----keçi sakalı

 East Anatolia and Blacksea region

 North and South Europe, North America and North Asia

FLORES SPIRAEAE ULMARIAE

(MEADOWSWEET)

 Phenol glycoside  MONOTROPITOSIDE---hydr.---methyl salicylate+gl+ks  Flavonoid---Spireoside (Quercetin 4’-O-glucoside)  Tannins  Essential oil O COOCH₃ Gl Ks MONOTROPİTOZİTMONOTROPITOSIDE

FLORES SPIRAEAE ULMARIAE

(MEADOWSWEET)

 Antirheumatic due to phenol glycoside

 Diuretic due to flavonoid content

 Methyl salicylate  antimicrobial, antipyretic and diuretic

 Commision E approved the use of the drug in cold, bronchitis and fever

IRIDOIDS

 Cyclopentanopyran main structure

 C1  OH

 The glycosidic bond is generally from the –OH on first position.

 There is a double bond between C3-C4.

 Number of C atom:

 8

 9 ---- substitution on C4 or C8

 10 --- substitution on both C4 and C8.

O OH 1 2 3 4 5 6 7 8 9

 -CH₃, -CH₂OH, -COOH, -CHO can be found as substituents.

 Besides, –OH, epoxide or lacton can also be found as substituent.

 Firstly isolated from an ant species,

“Iridomyrmex detectus” thats why they are called as iridoids!

 There can be a double bond on cyclopentane ring at 7-8 position

O OGl CH₂OH OH 1 2 3 4 5 7 8 9 DEKALOZIT (9 C'LU) 6 9 7 6 5 4 3 2 1 O 9 7 6 5 4 3 2 1 O 9 7 6 5 4 3 2 1 O OGl OH CH₃ COOCH₃ 8 MUSSENOZIT(10 C'LU) 11

IRIDOIDS

DECALOSIDE (9 C) MUSSENOSIDE (10C)

9 7 6 5 4 3 2 1 O OGl COOH OH CH₂OH 11 10 MONOTROPEOZIT ( 10 C'LU) 8 9 8 7 6 5 4 3 2 1 O OGl O O CH₂ COOCH₃ ASPERULOZIT 9 8 7 6 5 4 3 2 1 O OGl O CH₂OH O CO OH KATALPOZIT(9C'LU) 9 8 7 6 5 4 3 2 1 O O CH₂OGl HO CH₂OH C O CH₂ CH CH3 CH₃ 10 PATRINOZIT (10C'LU) MONOTROPEOSIDE (10 C) CATALPOSIDE (9C) PATRINOSIDE (10 C) ASPERULOSIDE

 They can found in nature as

monoglycosidic, diglycosidic or biosidic:

O OH CH₂OH OH OKUBIGENOL O OH CH₂OGl OGl 6 10 DIHETEROZIT O O CH₂OH OH seratinoz BIOZIT 1

IRIDOIDS

AUCUBIN BIOSIDIC GLYCOSIDE

 Non-glycosidic iridoids:

 Valepotriates found in Radix Valerianae

(valerian root)  (esters of isovalerianic acid) O OCOCH₂CH O _CH3 CH₂OCOCH₃ CHCH₂COO CH₃ CH₃ CH₃ 7 8 4 1 VALTRATUM

IRIDOIDS

 Secoiridoids  can be regarded as being

formed from iridoids by cleavage of the cyclopentane ring between C-7 and C-8 (e.g. Gentiopicroside)

DISTRIBUTION  SPERMATOPHYTA division  DICOTYLEDONAE class 1) APETALAE---Urticales--Eucommizceae 2) DIALYPETALAE--Geraniales-Meliaceae --Rosales--Saxifragaceae 3) SYMPETALAE—Apocynaceae/ Gentianaceae / Loganiaceae / Ericaceae / Caprifoliaceae / Labiatae / Scrophulariaceae / Verbenaceae etc.

IDENTIFICATION

1) Colourless; but they give blue colour in acidic medium.

2) Colouring and precipitation by TRIM-HILL reaction

 Trim-Hill Reagent consist of:

• 0.2% aqueous CuSO₄ (1 ml)

• CH₃COOH (10 ml)

• Conc. HCl (0.5 ml) mixture.

 Iridoids + Trim-Hill reagent  heat  firstly

blue or purple  than this coloured mixture

convert to a black precipitate in a few hours. 3) Chromatographic Assays:

 -TLC: Revelator ---- Vanillin-H₂SO₄ or Floroglusinol-HCl

 -HPLC

OBTAINING

 Since being not stable, fresh plant material is used for obtaining.

 The extraction medium shouldn’t be acid.

 Polar solvents are used for extraction

 Extract + washing by nonpolar solvents  liphophilic compounds will be removed

 Elimination of phenolic compounds and tannins by 1- Precipation using Pb acetate or 2- Eluting from activated charcoal / Al₂O₃.

 By eluting from polyamide column free

sugars and oligoholosides will be eliminated

 Seperated iridoids are isolated using chromatographic techniques.

QUANTITATIVE ANALYSIS

 GRAVIMETRIC

 COLORIMETRIC (Trim-Hill Reaction)

 CHROMATOGRAPHIC (GC and HPLC)

EFFECT AND USAGES

1) Compounds without strong effects 2) Traditionally used for years as;

 Insecticide

 Hypotensive

 Appetizer

 Tonic

3) Antimicrobial effect:

 - AUCUBIN---- not

effective----hydrolisis---AUCUBIGENIN (aglycone) or its dimer/ polymer----EFFECTIVE

 - ASPERULOSIDE (glycoside)---- not

effective ---hydrolisis----AGLYCONE----EFFECTIVE (against Staphylococcus

aureus; 600 I.U. Penicilline equivalent.

4) Purgative effect:  Due to -OH on 6. position  - free –COOH on 11. position decreases this effect

IRIDOIDS

11 O COOCH₃ OGl OH CH₃ MUSSENOZIT O OGl CH₂ O O COOCH₃ ASPERULOZIT O OGl CH₂OH OH 6 OKUBOZIT

IRIDOIDS

AUCUBIN MUSSENOSIDE ASPERULOSIDE

5) Diuretic effect: Catalposide 6) Analgesic and Antispazmodic  Harpagoside--- hydrolysis--- Aglycone---Antiphlogistic effect. 6 O OGl OH OH OH CH₃ 5 8 HARPAGOZIT

IRIDOIDS

HARPAGOSIDE

7) Appetizer and tonic effect: Loganoside 8) Sedative effect: Nonglycosidic iridoids---- Valepotriates 9) Antileukemic effect: Nonglycosidic iridoids O OGl OH CH₃ COOCH₃ 7 8 1 4 LOGANOZIT

IRIDOIDS

LOGANOSIDE

FLOS VERBASCI (EP)

 Scrophulariaceae – Verbascum sp. – Mullein

Drug is obtained from;

Verbascum phlomoides (Wooly mullein)

V. thapsus (great mullein/common mullein)

V. densiflorum (denseflower mullein) species.

 Known as «Sığır kuyruğu» in Turkish.

 Widely distributed in Europe, Africa, S. America and Turkey.

FLOS VERBASCI (EP)

1) Iridoid---- Aucubin---hydr.--- Aucubigenin + Gl

 Aucubigenin --- unstable ---

polymerize---browning.

2) Flavonoids --- Hesperidoside and Verbascoside

3) Mucilage 4) Saponin

FLOS VERBASCI (EP)

 Emollient

 Antitussive, expectorant

 German Comission E approved usage in

HERBA MONOTROPAE

 Monotropa hypopitys (Ericaceae)

 A parasitic plant living on Coniferae plants

 Common in Turkey

 Up to 10-30 cm hight, with scale-like leaves, yellowish-white coloured

HERBA MONOTROPAE

1) Iridoid glycosides---Monotropeoside  Monotropeoside  ---hydr.---Aglycone+Gl 2) Phenol gly.--- Monotropitoside---hydr.---Methyl salicylate+Gl+Xsy O OGl COOH OH CH₂OH 11 8 1 MONOTROPEOZIT COOCH₃ OGl Ks MONOTROPITOZIT MONOTROPEOSIDE MONOTROPITOSIDE

HERBA MONOTROPAE

 Drug;

 Antispasmodic

 Cough sedative

 Aglycone of Phenol glycoside---methyl

Galium Sp., Yoğurtotu, Bedstraw

 Galium aparine (cleavers, bedstraw)

(Rubiaceae)

 G. cruciata (star gentian)

 G. mollugo (hedge bedstraw)

 G. verum (lady's bedstraw)

 Well known in Europe, wide distributed

 Iridoid---- Asperuloside

 In Turkey; Gallium coronatum (Cruciata

taurica)----asperuloside and

monotropeoside; also rutoside is identified

 Antispasmodic

 Diuretic

 Antirheumatic

Plantago sp., Psyllium husk

 Plantaginaceae

 Plantago ovata (EP)

 P. lanceolata (EP)

 P. media

 Sinirli ot, sinir otu,

 20 species growing in: Europe, N. Africa,

 Stem and rosette leaves of the plant contain  Iridoid glycosides   Aucubin, catalposide O OGl CH₂OH OH 6 OKUBOZIT 6 O OGl CH₂OH COO O OH KATALPOZIT (%0.3-1.1)

Plantago sp., Psyllium husk

CATALPOSIDE

 Besides, leaves contain

Mucilage  arabinogalactan (2-6.5%)

Tannin (6.5%)

Phenolic carboxylic acids  protocatechuic acid

Flavonoids

Minerals (Zn, K)

Traditionally;

 Antiinflammatory

 Fresh juice or plaster prepared from the

juice is used against itch caused by insect bites

 Infusion  used as eyewash against

inflammations in the eyes

 Used as mouthwash against throat inflammation

 Cicatrizan in skin diseases

 Used also against cough, bronchitis, upper respiratory infections

 Plantago psyllium, which is well known in

Turkey, used as laxative and emollient regarding mucilage content