kuliah farmakognosi alkaloids 2
TRANSCRIPT
Chemical properties The substitution on the nitrogen atom
The state of the alkaloid
R
NH2
R
HN
R2 R
N
R3
R2
R
N
R4
R2
R3+
Cl-1ry 2ry 3ryquaternary
R
NH2
R
N
R3
R2
R
NH3
Cl-
+O
Free base
Salt formN-oxide
Classification Non-heterocyclic or atypical alkaloids or biological
amines
Heterocyclic or typical alkaloids: divided into groups according to their ring structure
H3CO
H3CO
OCH3
CH2 CH2
NH2
Mescaline
N
H
N
H
N
N
pyrrole pyrrolidine pyrrolizidine pyridine
HN
NMe
N
N
piperidine tropane quinoline isoquinoline
NH N
H
N
NH
NMeindoleindolizidine imidazole
aporphine
N
N
H3CO
HO
H H
N
N
H3CO
HO
H H
89
Quinine Quinidine
NMe
OH CH2OH
(-) hyoscyamine
N
OH CH2OH
(-) hyoscine (scopolamine)
Me
O
NMe
OH
tropine O
O
EFEK FARMAKOLOGI ALKALOID
1. Analgetik dan narkotik : morfin 2. Alkaloid jantung : alkaloid kinidin dan
spartein (Erytropleum guineense) 3. alkaloid yg mempengaruhi peredaran
darah dan pernafasan : Veratrum, Rauwolfia (hipotensi), lobelia (lobelin murni obat asma)
4. kemoterapetik dan antiparasit (kina, areca dan granatum (anticacing),
5. stimulan uterus : secale alkaloid (Hydrastis), alkaloid benzilisokinolin (berberis)
6. anastetik lokal (cocain) 7. midriatika : belladona dan alkaloid coca.
AlkaloidTropan Ester alkaloid : asam organik + amino alcohol (Basa). The parent base is the “Tropane” base.
Alkaloid Tropane dikelompokan mjd:
1- Solanaceous Tropane Alkaloids.
2- Erythroxylon (Coca) Alkaloids.
HN
12
34
56
7NH
1- Solanaceous Tropane Alkaloids
Terdapat:Atropa, Datura, Hyoscyamus, Duboisia spp.
Alkaloid utama:1- Atropine.
2- Hyoscyamine.
3. Hyoscine (Scopolamine).
Atropine & Hypscyamine Hyoscyamine is the major natural alkaloid with
negative optical rotation (l- form). During extraction hyoscyamine racemizes to the
optically inactive dl Atropine. Both alkaloids composed of tropine base and tropic
acid.
NCH3 O
OHO
N
O
Me
O
H CH2OHN
O
O
CH2OHMe
Atropine(-)-Hyoscyamine
Tropine base
Tropic Acid
*
Hyoscine (Scopolamine) Hyoscine is an ester of l-tropic acid with scopoline
base. Hyoscine is a syrupy liquid.
NCH3 O
OHO
O
Scopoline base
Tropic Acid
Khasiat dan aksi farmakologi:The three Alkaloids are anticholinergic agents: Decrease saliva and GIT secretions so used preoperative. Decrease motility of smooth muscles so used as
antispasmodics. Stimulate respiratory system. A mydriatic (causes dilatation of the eye pupil).
An antidote to organophosphorus insecticides. Hyoscine has more central effect so it is sedative and hypnotic. Hyoscine is mainly used as antiemetic.
2- Erythroxylon (Coca) Alkaloids
Occurrence:Coca leaves contain about 2% total alkaloids.
Main Alkaloids are:1- Cocaine.
2- Cinnamylcocaine.
3. a- truxilline.
The base for Coca Alakloid is called “Ecogonine”
NH3C OH
C
O
OH
Ecogonine
It is the major Alkaloid in Coca leaves. Cocaine is diester Alkaloid. Heating at 160 0C in conc. HCl leads to hydrolyses of
cacaine to MeOH, Benzoic acid and Ecogonine base.
NCH3 O
O
COOMe
Benzoic acid
Ecgonine base
Cocaine
Production of Cocaine commercially: The total Alkaloids are hydrolysed to obtain the free base. The base is then Methylated with HCl in MeOH. The Methylated base is then esterified with Benzoly
chloride.
Cinnamylcocaine
NCH3 O
O
COOMe
Cinnamic acid
Ecgonine base
Uses:Cocaine was used as local anesthetic.
Cocaine has a CNS stimulant activity so is one of the widely abused drugs.
Catharanthus :Vinca
Catharanthus roseus
Family : Apocynaceae
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Perennial or annual herbaceous plant 40-60cm .
The leaves have acute base , rounded apex and have entire margin .
The flowers are rose or violet or white or white with red eyes .
The fruits have slight odour with bitter taste .
The leaves have very strong and unpleasant odour and taste.
origin : Australia, Madagascar also cultivated in Tropical Africa .
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Biochemical constituents
Alkaloid indole group :1. Vincristine 2. Vinblastine3. Vindoline (inert)4. Catharanthine (inert)500kg of Catharanthus plant used to
isolate 1g vincristine Main slide
Therapeutic uses Anti-neoplastic activity
(anti tumer)Used for treatment of
leukemia in children.
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Medications
1. Vincristine ®-Vials- Abic 2. Oncovin® - Vincristine – Vials-Lily 3. Velbe ® -Vinblastine – Vials-Lily
(Hodgkin´s disease )4. Blastovine® -Vinblastine-Teva –
Vials.All of these drugs present as
sulphate salts.
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