kuliah farmakognosi alkaloids 2

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

NH

O

pelletierine

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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