Sesterterpenes C25H40

Obtained of condensation 5 IPP by head-to-tail manner; structural variations [lactones]

GGPP + IPP→Sesterterpenes (Ophiobolanes)Isolated as phytotoxic principles from pathogenic fungiIsolated from marine organisms, spongesAntibacterial, antifungal, antinematodal activities

Triterpenes

• MVA-derived• Tail to tail of 2 x FPP• 1st Isolated from shark

(Squalus sp.), later from rat liver & yeast

• Many seed oils rich in squalene

OPP

OPP

FPP

Allylic cation

FPP

H H

Squalene

Squalene Synthase

Squalene Synthase

NADPH

Squalene C30H50

Different folding possibilitiesCyclisation and rearrangement:Triterpenes:-Tetracyclic triterpenes-Pentacyclic triterpenes (Lupeol type, α- and ß-

amyrin types)Steroids: (Sterols, bile acids, steroid hormones,

steroid saponins, steroid alkaloids, cardiac glycosides, Vit. D )

Lanatosterol & Cycloartenol

• Oxidation, cyclyzation, alkyl migration & folding of squalene produce STEROIDS {lanosterol (animals & fungi) and cycloartenol (plants)}

• Natural triterpenes & steroids OH at C3

H H

Squalene

O

23

HO

Squalene oxide

LanosterolAnimals & Fungi

HOCycloartenol Plants

Tetracyclic and pentacyclic triterpenes

A B

C D

HOA B

CD

HO

A B

CD

HO

EE

E

Alpha- Amyrin Beta-Amyrin Lupeol

1717

17

Dammarane

Saponins Many triterpene have been isolated. Few of medicinal interest,

mainly saponins Common Characters of SAPONINS: Glycosides (mono- or bis-desmosides) Produce stable froth in aqueous solution (shaking) Surfactant effect (oil-H2O mixes) Surfactant effect (soap-like) Latin origin: sapo=soap. Saponins-

rich plants were used for cleansing e.g. soapwort (Saponaria officinalis, Caryophyllaceae), Quillaia or soapbark (Quillaja saponaria, Rosaceae)

Induce RBC haemolysis (changes wall permeability) PPt by heavy metals e.g. Mg, Hg, Pb....

Saponins cont.

Tetra- or Penta-cyclic structuresSteroidal of triterpenoidal nucleusToxic to cold-blooded animals (fishing,

pesticides, molluscosides)Induce RBC haemolysis (changes wall

permeability)Arrow poison (RBC haemolysis)

Chemistry of Triterpenoid Saponin

25

AB

CD

E

1

2

34 5

67

89

10

11

1213

14

1516

1718

19

20

21

22

2324

26

27

28

29 30

HO

O

O

O

O

O

O = Oxygenation site

Liquorice

• Unpeeled rhizomes and roots of the perennial herb Glycyrriza glabra, Fabaceae

• Russian liquorice peeled prior to drying, G. glabra var.glandulifera

• Chinese spp. G. uralensis (Manchurian liquorice) commercially valued

• Water extracted, dried by evaporation producing black solid

Medicinal and Economic Applications of Liquorice

• Flavouring agent (food, tobacco, beers, chewing gums)

• Sweet, froth forming (saponins characters) Glycyrrhizin 50-150x ≥ sweet sugar (bitter taste mask) pharmacy

• Demulcent, surfactant, expectorant, laxative

• Corticosteroid-like activity, mild anti-inflammatory, mineralocorticoid activity

• Rx Addison’s disease, # catalyse enzyme prevent conversion of PG & glucocorticoides into inactive metabolites (inc. PGE2, PGF2 & HC) (Cushing’s S/E)

Chemical Composition

12% water extractives

3-5% glycyrrhizic (glycyrrhizinic) acid

1-1.5% free & glycosidic flavonoids (yellow colour)

5-15% sugars (glucose & sucrose)

CO2H

O

OO

OH

OHHO2C

CO2H

OH

HOOH

O

O17

12

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Glycyrrhetic Acid= Glycyrrhetinic Acid

D-Glucuronic Acid

Glycyrrhizic Acid=Glycyrrhizinic acid

D-Glucuronic Acid

Semi-Synthetic Derivatives of Glychyrrhizic acid

• Hemisuccinate Carbenoxolone Na, semisynthetic derivative of glycyrrhetic acid for Rx gastric & duodenal ulcers (inc. Na + dec. K S/E)

CO2

O

1712O

O2C

O 2Na

Carbenoxolone Sodium

Panax ginsengRoots (Araliaceae)

• China, Korea & Russia• Other related Panax spp. • P. quinquefolium (American ginseng) USA & Canada • P. notoginseng (Sanchi-ginseng) ChinaPan=all (Gr) akos =remedy (Gr) →→ “Universal remedy”

جينسنغ

Biological Activities of Ginseng

Traditional remedy in China & Russia:Rx of anaemia, diabetes, gastritis, insomnia,

sexual impotenceGeneral restorative, promoting health and

longevityWhite ginseng (peeled roots)Red ginseng (steamed roots) reputed

enhancing biological activity

PharmacologyClassified as ADAPTOGEN = agent helps the body to adapt to

stress (physical/ chemical/ biological stress)Unspecific enhancement of the body’s resistance to exogenous stress or noxes Improve stamina & concentration Provides a normalizing & restorative effect Promoted as an aphrodisiac Korean root is best Most expensive Long term use lead to corticosteroid poisoning symptoms e.g.

HTN or hypotension, nervousness, sleeplessness, tranquilizing effects [ginseng-abuse syndrom]

Antioxidant Affect both CNS & neuroendocrine functions Alter lipid & carbohydrate metabolism Modulate immune functions??

Chemistry• Triterpenoid saponins (30 ginsenosides )• Ginsenosides (Japanese) or Panaxosides (Russians)• Panaxosides A, B,D, E,…. • Derivatives of Protopanaxadiol (aglycone) or

Protopanaxatriol (aglycone)• Rb1 is the most abundant Diol series

• Rg1 major representative of the Triol esters

• Red ginseng is rich in partially hydrolysed esters & glycosides (inc. antioxidant phenolics)

• White ginseng ginsenosides as esters

Panaxadiols

Gly1 Gly2

Ginsenoside Rb1 B1 2- Glc-Gluc B1 6-Gluc-Gluc

Ginsenoside Rb2 B1 2- Glc-Glu B1 6-Ara-Glc (pyranose)

Ginsenoside Rc B1 2- Glc-Glu B1 6-Ara-Glc (Furanose)

Ginsenoside Rd B1 2- Glc-Glu Glc

Gly1O

HO OGly2

63

20

Ginsenoside (Panaxoside)

H+

HO

HO OH

63

20S-Protopanaxadiol

H+

HO

HO

63

2020

20S-Panaxadiol

O

Panaxatriols

HO

OHOGly2

OGly1

63

20

Ginsenoside (Panaxoside)

Gly1 Gly2

Ginsenoside Re B1 2- Rha-Gluc Gluc

Ginsenoside Rf B1 2- Glc-Glc H

Ginsenoside Rg1 Glc Glc

Ginsenoside Rg2 B1 2- Rha-Glc H

H+

HO

OHOH

OH

63

20S-Protopanaxatriol

H+

HO

HO

OH

63

2020

20S-Panaxatriol

O

Dosage & Standardization

• PO 100-600mg/day in divided doses • Standardized product to contain minimum of

5% ginsenosides/ doseRegimen for maximum efficacy:4 weeks on, followed by 2 weeks off

Siberian or Russian Ginseng Eleutherococcus senticosus

• Inexpensive alternative to Panax spp • Roots, family Araliaceae

Eleutherococcus senticosus

• Adaptogen • Eleutherosides (diff. chemical classes)• Eleutheroside E =syringaresinol diglucoside (main)

lignan glycoside• Eleutheroside B = syringin (phenylpropane glycoside)• PO 100-200mg BID• Standardized 0.8% eleutherosides B & E/dose• 4 weeks on, 2 weeks off

Eleutherosides

OH

OCH3

Glc-O

H3CO

OCH3

Glc-O

H3COO

O

OCH3

O-Glc

OCH3

Syringaresinol diglucoside (Eleutheroside E)

Syringin(Eleurtheroside B)