2. b tropane alkaloids

7/21/2019 2. b Tropane Alkaloids

http://slidepdf.com/reader/full/2-b-tropane-alkaloids 1/62

Presentation for

Class: Fifth Semester B. Pharm

Subject: Pharmacognosy (250006)

Topic: Tropane Alkaloids

Prepared by: Dr. U. M. Upadhyay

Designation: Principal

College: Sigma Institute of PharmacyAt. Bakrol, Ta. Waghodia, Dist. Baroda

College code: SIP (261)



Alkaloids are cyclic organic compounds

containing nitrogen in a negative state of

oxidation with limited distribution among

living organisms.



Distribution and occurrence:• Rare in lower plants.

• Dicots are more rich in alkaloids than

Monocots.

• Families rich in Alkaloids: Apocynaceae,

Rubiaceae, Solanaceae and Papaveracea.

• Families free from Alkaloids: Rosaceae,

Labiatae



Distribution in Plant:

• All Parts e.g. Datura.

• Barks e.g. Cinchona

•

Seeds e.g. Nux vomica• Roots e.g. Aconite

• Fruits e.g. Black pepper

• Leaves e.g. Tobacco• Latex e.g. Opium



Psychoactive alkaloids

Stimulants Hallucinogens Depressants

Cocaine Tropane alkaloids Morphine

Ephedrine Mescaline Codeine

Caffeine Psilocybin Heroin

Ergot alkaloids (LSD)



Tropane alkaloids

Many of these psychoactive alkaloids



Tropane Alkaloids• They are ester alkaloids resulted from the coupling of

organic acids with amino alcohol (Base). Derived fromtropine and consist of mandelic, tropic or benzoic acidesters of tropine.

• The parent base is the “Tropane” base.

• Tropane Alkaloids are classified into:

1- Solanaceous Tropane Alkaloids.

2- Erythroxylon (Coca) Alkaloids.

HN1

2

34

56

7NH



1- Solanaceous Tropane Alkaloids

• Occurrence: Atropa, Datura, Hyoscyamus, Duboisia spp.

• Main Alkaloids are:1- Atropine.

2- Hyoscyamine.

3. Hyoscine (Scopolamine).



Atropine & Hyoscyamine

• 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 CH2OH

N

O

O

CH2OHMe

Atrop ine (-)-Hyoscyamine

Tropine base

Tropic Acid

*



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.

Hyoscyamine



Atropine

• Atropine is a core medicine in the World HealthOrganization's "Essential Drugs List", which is a list ofminimum medical needs for a basic health care

system.• Atropine is a racemic mixture of D-hyoscyamine and

L-hyoscyamine.

• The most common atropine compound used in

medicine is atropine sulfate .• Atropine sulfate Injection, USP

0.1 mg/mI (Adult)0.05 mg/mL (Pediatric)

http://en.wikipedia.org/wiki/World_Health_Organization

http://en.wikipedia.org/wiki/WHO_Model_List_of_Essential_Medicines





http://en.wikipedia.org/wiki/Racemic

http://en.wikipedia.org/wiki/Hyoscyamine

http://en.wikipedia.org/wiki/Sulfate



http://en.wikipedia.org/wiki/Hyoscyamine

http://en.wikipedia.org/wiki/Racemic






Pharmacological Action of Atropine

• A mydriatic (causes dilatation of the eye pupil).

• An antispasmodic (relaxes the intestinal and

bronchial smooth muscles).

• A preanesthetic medication to stop body

secretions.

• A CNS stimulant.

• An antidote to organophosphorus insecticides.



Side Effects of Atropine

Adverse reactions to atropine include:

• ventricular fibrillation.

•

tachycardia.• dizziness.

• nausea.

• blurred vision & dilated pupils• loss of balance, & confusion.

http://en.wikipedia.org/wiki/Fibrillation

http://en.wikipedia.org/wiki/Tachycardia

http://en.wikipedia.org/wiki/Vertigo_(medical)

http://en.wikipedia.org/wiki/Nausea

http://en.wikipedia.org/wiki/Confusion

http://en.wikipedia.org/wiki/Confusion

http://en.wikipedia.org/wiki/Nausea

http://en.wikipedia.org/wiki/Vertigo_(medical)

http://en.wikipedia.org/wiki/Tachycardia

http://en.wikipedia.org/wiki/Fibrillation



NH3C

O

O

HO NH3C

O

H CH2OH

O

(-)-Hyoscyamine

Atropine

(-)-Hyoscine

Solanaceous Alkaloids



Natural Source of Atropine & Hyoscine

• Atropine & Hyoscine are tropane alkaloids

extracted from deadly nightshade ( Atropa

belladonna), jimsonweed (Datura

stramonium), Duboisia(Duboisia myobroides),

henbane (hyoscyamus niger & hyoscyamus

muticus) and other plants of the family

Solanaceae.

http://en.wikipedia.org/wiki/Tropane

http://en.wikipedia.org/wiki/Alkaloid

http://en.wikipedia.org/wiki/Deadly_nightshade

http://en.wikipedia.org/wiki/Jimsonweed

http://en.wikipedia.org/wiki/Solanaceae

http://en.wikipedia.org/wiki/Solanaceae

http://en.wikipedia.org/wiki/Jimsonweed

http://en.wikipedia.org/wiki/Deadly_nightshade

http://en.wikipedia.org/wiki/Alkaloid

http://en.wikipedia.org/wiki/Tropane



Natural Sources of Atropine & Hyoscine

Atropa belladonna

( Solanaceae)

Hyoscyamus niger ( Solanaceae)

Datura stramonium

http://images.google.com/imgres?imgurl=http://caliban.mpiz-koeln.mpg.de/koehler/DATURA.jpg&imgrefurl=http://caliban.mpiz-koeln.mpg.de/~stueber/koehler/&usg=__aUhUBQGdqx6utVHKO17N4dVW_CY=&h=2166&w=1727&sz=1143&hl=en&start=10&sig2=1ioZ3GxfRWIizfbluiKyGA&um=1&tbnid=jly3eOAZkWdJWM:&tbnh=150&tbnw=120&prev=/images?q=datura+stramonium&hl=en&safe=active&um=1&ei=v_7-Ssi_JJCy6wOHk_XrCg

http://images.google.com/imgres?imgurl=http://cache3.asset-cache.net/xc/89179524.jpg?v=1&c=IWSAsset&k=2&d=17A4AD9FDB9CF193334E6B5204AF254C119303A51516F8E3E30A760B0D811297&imgrefurl=http://www.gettyimages.com/detail/89179524/De-Agostini&usg=__k3y0siGNw0ryfXjOhXcGMTImiwY=&h=594&w=439&sz=34&hl=en&start=5&sig2=0317HZb9p7oq6c8y77gdog&tbnid=BtGsK-wSP894NM:&tbnh=135&tbnw=100&prev=/images?q=hyoscymus+plant&gbv=2&hl=en&safe=active&sa=G&ei=34r-Sq2UH4qi-Aa_5ZntCg

http://www.botanical.com/botanical/mgmh/n/nighde05-l.jpg



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



Hyoscine (Scopolamine)

• Hyoscine is an ester of l -tropic acid with scopoline base.

• Hyoscine is a syrupy liquid.

Hyoscine



Plant material and solvent

Extract

Concentration

Acidified Extract (Alk. as salts)

Organic solvent dissove Impurities

Acidification

Alkalinization

Alkaline aqueous layer

Organic solvent dissove Alkaloids



Separation of the Alkaloidal mixtures:

Alkaloids in the form of HCl salts

1- Alkalinize by NaHCO3

pH 7.5

2- Extract with Ether

Ether

Hyoscine free base

(pKa = 6.2)

Aqueous layer

Atropine & Hyoscyamine HCl

(pKa = 9.3)

Convert to oxalate salts,

Fractional Crystallization

(Acetone/ Ether)

Atropine Oxalate

CrystalsHyoscyamine Oxalate

Solution



Atropine & Hyoscyamineine Oxalates

Crystallization from

Acetone/Ether

Atropine Oxalate

Crystals

Hyoscyamine Oxalate

Solution



Chemical tests:

• Vitali-Morin’s test:

Solid alkaloid + fuming HNO3 → Evaporate to dryness, dissolveresidue in acetone, add methanolic solution of KOH → Violet

colour.

• P-dimethylaminobenzaldehyde:

Alkaloid + reagent in porcelain dish and heat on boiling water path→ Intense Red Colour → Cherry Red after cooling.

• Gerrard’s test:

Alkaloid + 2% HgCl2 in 50% Ethanol →

Red colour Atropine

Red after warming Hyoscyamine

White ppt Hyoscine



Pharmacological actions and uses:

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.



Synthetic and Semisynthetic Derivatives:

• Homatropine:

Synthetic drug prepared by passing HCl gas in a mixture of tropinebase and mandelic acid in the presence of water.

Homatropine is less toxic than Atropine. It is hypnotic in small

doses. Homatropine is used as Mydriatic with shorter effect thanAtropine.

NCH3 O

OHO



• Hyoscine butyl bromide:

Quaternary Semisynthetic derivative of Hyscine.

It is used as antispasmodic and antiemetic.

NCH3 O

OHO

O Bu+

Br-



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”

N

H3C OH

C

O

OH

Ecogonine



Erythroxylon cocca



• 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:



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 oneof the widely abused drugs.



Hyoscine



Datura stramonium - Solanaceae

Definition: Stramonium Leafconsists of the dried leavesor dried leaves andflowering tops of Daturastramonium. The drugshould contain at least0.25% alkaloids calculatedas hyoscyamine.

Common names: Stramoniumleaf, Thornapple, Jimson orJamestown weed



Datura stramonium



Datura stramonium - Constituents

Main (Tropane) Alkaloids

* Hyoscyamine

• Hyoscine (2:1)

Younger plants: hyoscine –

predominant alkaloid

Also contains

• Atropine

• Larger stems contain littlealkaloid, and drug shouldcontain no more than 3% ofstems with a diameter >5mm



Datura stramonium – Allied Drugs &

Adulterants

ALLIED DRUGS

Datura innoxia

Datura metel (dried leaves

are also curled andtwisted – like D.

stramonium), but are

browner in colour.

Datura sanguinea

ADULTERANTS

Xanthium, Carthamus and

Chenopodium leaves

(easily distinguished fromoriginal herb)



Uses of Datura stramonium

Atropine: Stimulant on CNS

Depresses nerve endings onthe secretory glands andsmooth muscle

Hyoscine: lacks CNS stimulantaction of atropine

Sedative – motion sickness

Atropine & Hyoscine: used inopthalmic practice to dilatethe pupil of the eye.



Hyoscyamus niger - Solanaceae

Definition: Hyoscyamusleaf consists of thedried leaves or driedleaves and flowering

tops of Hyoscyamusniger . It should containat least 0.05% alkaloids

– hyoscyamine.

Common names:Henbane



Hyoscyamus niger - Constituents

Tropane Alkaloids

Mainly

• Hyoscyamine

• Hyoscine (main

constituent)



Hyoscyamus niger – Allied Drugs

• Hyoscyamus albus(petiolate stem-leaves andpale yellow, non-veined

petals – bottom left).• Hyosycamus muticus (top

right)

• Hyoscyamus pusillus

• Hyoscyamus aureus

• Hyoscyamus reticulatus

(Indian henbane – bottomright)



Hyoscyamus niger - Uses

Resembles belladonna

and stramonium in

action – only weaker.

Higher hyoscine content –less likely to cause

cerebral stimulation .

Used to relieve spasm of

the urinary tract



Hyoscyamus niger



Hyoscyamus niger - flower



Atropa belladonna - Solanaceae

Definition: Belladonna herbconsists of the dried leavesand flowering tops of

Atropa belladonna,containing at least 0.3%alkaloids (hyoscyamine).

Should not contain >3% stem>5mm in diameter.

USP also allows A. acuminatain the Belladonna Leafmonograph.



Atropa belladonna - Constituents

Main (Tropane) alkaloid

• Hyoscyamine

Also contains

• Scopoletin

• Calcium oxalate



Atropa belladonna

ALLIED DRUGS

Indian belladonna ( Atropaacuminata) – yellow-brown flowers &

brown-green leaves.

Atropa baetica (yellowflowers and blackberries) – endangeredspecies

ADULTERANTS

Phytolacca decandra

Ailanthus glandulosa



Atropa belladonna - Uses

Used as a sedative

To stop bodily secretions

(e.g. saliva)

Root preparations areused externally



Atropa belladonna



Withania somnifera• B.S. - Dried Roots and Stems of Withania

somnifera

• Family – Solanaceae

• C.C. –

– Steroidal Lactone

Withanolide A, Withanolide B

– Alkaloids –

Anaferine, Withanine, Tropine• Chemical Test – It gives Vitali-Morin Test.

• Use - Immunomodulator

It is known as Indian Ginseng.



Withania somnifera



Duboisia myoporoides

• B.S. - Dried Leaves of Duboisia myoporoides

• Family – Solanaceae

• C.C. – Atropine

Scopolamine

• Chemical Test – It gives Vitali-Morin Test.

•

Use - Parasympatholytic



Duboisia

myoporoides

2. b tropane alkaloids

Documents