Sesterterpenes C 25 H 40
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Transcript of Sesterterpenes C 25 H 40
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)