This document discusses tropane alkaloids, specifically atropine alkaloid. It summarizes that atropine alkaloid is mainly found in plants from the solanaceae family, like Atropa belladona and Datura stromonium. It then describes the isolation, biosynthesis, identification tests, chemistry and properties, structure-activity relationships, uses, and mechanism of action of atropine alkaloid.

1. TROPANE ALKALOIDS
Kratika Daniel (Ph.D)
Assistant professor
MANDSAUR INSTITUTE OF PHARMACY,
Mandsaur
KRATIKA
8/30/2012 Kratika Daniel (Ph.D) 1
Assistant professor
MANDSAUR INSTITUTE OF PHARMACY

2. TROPANE ALKALOIDS
COCAINE ALKALOID
ATROPINE ALKALOID
 Atropine alkaloid is mainly found in member of solanaceae family in
different concentration: -
 Atropa belladona (0.4 – 1%)
 Datura stromonium (0.2%)
 Hyosymus niger (0.05%)
• Other solanaceous alkaloid are Hyosyamine, Hyoscine (Scopolamine),
Apoatropine, Belladonine.
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3. ISOLATION
Powdered drug/ juice + moisten drug
with aqueous solution of K2CO3
Extract with CHCl3
Evaporate solvent
Extract with Dil. H2SO4
Acidic extract made alkaline by K2CO3
Atropine precipitate out
Crystallize by use of alcohol
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4. BIOSYNTHESIS
COOH
NH2 CHCOOCH3
acetate phenylalanine
H3C N CHOCOC6H5
NH2 CH2
Ornithine Cocaine
COOH
STEP - 1 decarboxylation
NH2 NH2
NHCH3 NHCH3
δ- N - methyl ornithine N - methyl putrescine
oxidation
acetoacetic acid +
N CH3X
CHO
N - methyl - δ − pyrrolinium salt NHCH3
4-(methylamino)butanal
N CH3 O +
N CH3 O aldol N CH3 O
dehydrogenation condensation
hygrine
tropinone
reduction
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CH Daniel (Ph.D)
OH 4
tropine

5. STEP 2
COOH O
OH COOH
HO OH NH2 O
OH
shikmic acid phenyl alaine phenyl pyruvic acid
COOH
C CH2OH
H
tropic acid
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6. STEP - 3 COOH
C CH2OH + N CH3 OH
H
tropine
tropic acid
heat HCl
O CH2OH
N CH3 O C CH
Atropine/ Hyosyamine
HC OCO CH N CH3 O
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CH2OH scopolamine

7. Identification test
1.(Vitali – Morin reaction): -
Alkaloid/ atropine
(1µg)
+ Drop of H SO 2 4 Evaporate to dryness
Indicates Which produce Add 0.3ml of 3% solution of
presence
of atropine bright purple color KOH in methyl alcohol
2. On addition of AgNO3 solution to solution Yellowish
of hyoscine hydrobromide white ppt
Insoluble – HNO3
Soluble – Dil. NH3
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8. General Test For Alkaloids
 Mayer reagents : - (potassium mercuric iodide solution)
give white ppt.
 Dragondroff’s reagent: - (KI + bismuth nitrate)
orange red ppt
 Wagner’ s reagent: - (iodine solution)
brown ppt.
 Hager’s reagent: - (saturated solution of picric acid)
crystalline yellow ppt.
 Freshly prepared solution of tannic acid (5%w/v) buff ppt
insoluble in NH3
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9. TLC
• 1% solution of atropine dissolved in 2N acetic acid is
spotted over silica gel G plate and eluted in the solvent
system of strong NH3 solution – methanol (! : 5 : 100).
• TLC plate is spread with an acidified iodoplatinate solution.
•Rf – 0.18.
•Solvent system – Acetone – 0.5 sosium chloride solution.
•Spraying reagents – Dragondroff’s reagent.
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10. Chemistry & Properties
•Melting point – 115oC to 116oC.
•Molecular formula – C17H23NO3
•On hydrolysis it gives alcohol, tropine, and tropic acid which
indicates that atropine is an ester.
C17H23NO 3 + H2O C8H9NO + C19H10O 3
atropine tropine tropic acid
•It is optically inactive (±) atropine is racemate form of
hyoscyamine.
• Solubility – Insoluble in ether.
Easily soluble in chloroform, alcohol.
Sparingly soluble in water.
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11. SAR
H2C CH CH2 O
H3C N HC O C CH
H2C CH CH2 CH2OH
1. The primary part of attachment to cholinergic sites is through the
positively charged nitrogen (cationic head).
* In tertiary amines, they are quaternized by protonation at physiological
pH which causes lack of CNS activity.
2. For hydrophobic bond formation & vander waal interaction on aryl
group (phenyl thienyl) & a cycloaliphatic (cyclohexyl) is necessary.
3. The presence of free hydroxyl or carbamide is also importat for
hydrogen bonding with receptor.
4. L – hyoscyamine is more active than d- isomer.
5. Difference b/w hydroxyl group & quaternqry nitrogen is b/w 2o to 3o.
6. It has similar structure to acetylcholine but contain additional
substituent which enhance bindig to receptor.
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12. 7. It has acetic acid ester of amino alcohol which is therapeutically
useful.
Minimal structure necessary for pure atagoistic activity is due to
H5C6 O
CH C O CH2 CH2 N(R')2
R
R = hydroxy alkyl, alkyl, cycloalkyl, or heterocyclic
R’ = alkyl.
8. The high potency of ester and amides of tropic acid result from their
ability to H – bond with suitable group o the receptor, surrounded by
hydrophobic area.
CH2OH H5C2
CH C N CH2 N
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13. USES & ACTION
1.It has stimulant action on CNS & depress the
nerve ending to the secretor glands.
2.It is useful in ophthalmic products b/c it
dilates the pupil of eye (mydrasis).
3.Antispasmodic action – GIT motility is
inhibited & gastric secretion is inhibited.
4.CVS – alters heart rate, stimulation of vagus
nerve, bradycardia.
5.Inhibition of secretion – Salivary, Lachrymal,
Bronchial, & Scrotal gland.
Producing an uncomfortably dry mouth & skin.
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