Tropane alkaloids notes

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

2. 8/30/2012 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 areHyosyamine, Hyoscine (Scopolamine),
Apoatropine, Belladonine.
Kratika Daniel (Ph.D)

3. 8/30/2012 3
ISOLATION
Powdered drug/ juice + moisten drug
with aqueous solution of K
2CO
3
Extract with CHCl
3
Evaporate solvent
Extract with Dil. H
2SO
4
Acidic extract made alkaline by K
2CO
3
Atropine precipitate out
Crystallize by use of alcohol
Kratika Daniel (Ph.D)

4. 8/30/2012 4
BIOSYNTHESIS
COOH
NH
2
NH
2
Ornithine
NCH
3
CH
2
CHCOOCH
3
CHOCOC
6
H
5
Cocaine
phenylalanineacetate
COOH
NH
2
NHCH
3
δ- N - methyl ornithine
decarboxylation
NH
2
NHCH
3
N - methyl putrescine
oxidation
CHO
NHCH
3
4-(methylamino)butanal
NCH
3
X
+
N - methyl - δ − pyrrolinium salt
acetoacetic acid
NCH
3 O
hygrine
dehydrogenation
N
+
CH
3 O
NCH
3 Oaldol
condensation
tropinone
reduction
NCH
3 OH
tropine
STEP -1
Kratika Daniel (Ph.D)

5. 8/30/2012 5
COOH
OH
OH
OH
shikmic acid
O
NH
2
OH
phenyl alaine
O
COOH
phenyl pyruvic acid
CCH
2
OH
H
COOH
tropic acid
STEP 2
Kratika Daniel (Ph.D)

6. 8/30/2012 6
CCH
2
OH
H
COOH
tropic acid
NCH
3 OH
tropine
+
HCl
NCH
3 OC CH
O CH
2
OH
Atropine/ Hyosyamine
NCH
3OCHOCO
CH
CH
2
OH
scopolamine
heat
STEP -3
KratikaDaniel (Ph.D)

7. 8/30/2012 7
Identification test
1.(Vitali –Morin reaction):-
Alkaloid/ atropine
(1µg)
+Drop of H
2SO
4 Evaporate to dryness
Add 0.3ml of 3% solution of
KOH in methyl alcohol
Which produce bright purple color
Indicates presence of atropine
2. On addition of AgNO
3solution to solution
of hyoscine hydrobromide
Yellowish white ppt
Insoluble – HNO
3
Soluble – Dil. NH
3
Kratika Daniel (Ph.D)

8. 8/30/2012 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 NH
3
Kratika Daniel (Ph.D)

9. 8/30/2012 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 NH
3solution –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.
Kratika Daniel (Ph.D)

10. 8/30/2012 10
Chemistry & Properties
•Melting point – 115
o
C to 116
o
C.
•Molecular formula –C
17H
23NO
3
•
On hydrolysis it gives alcohol, tropine, and tropic acid which
indicates that atropine is an ester.
C
17
H
23
NO
3+
H
2
O C
8
H
9
NO +C
19
H
10
O
3
tropine tropic acidatropine
•It is optically inactive (± ) atropine is racemate form of
hyoscyamine.
•Solubility –Insoluble in ether.
Easily soluble in chloroform, alcohol.
Sparingly soluble in water.
Kratika Daniel (Ph.D)

11. 8/30/2012 11
SAR
CH
2
CH
2
CH
CH
CH
2
CH
2
NCH
3
CH O CCH
O
CH
2
OH
1.Theprimarypartofattachmenttocholinergicsitesisthroughthe
positivelychargednitrogen(cationichead).
*Intertiaryamines,theyarequaternizedbyprotonationatphysiological
pHwhichcauseslackofCNSactivity.
2.Forhydrophobicbondformation&vanderwaalinteractiononaryl
group(phenylthienyl)&acycloaliphatic(cyclohexyl)isnecessary.
3.Thepresenceoffreehydroxylorcarbamideisalsoimportatfor
hydrogenbondingwithreceptor.
4.L–hyoscyamineismoreactivethand-isomer.
5.Differenceb/whydroxylgroup&quaternqrynitrogenisb/w2
o
to3
o.
6.
Ithassimilarstructuretoacetylcholinebutcontainadditional
substituentwhichenhancebindigtoreceptor.
KratikaDaniel (Ph.D)

12. 8/30/2012 12
7.It has acetic acid ester of amino alcohol which is therapeutically
useful.
Minimal structure necessary for pure atagoistic activity is due to
R = hydroxy alkyl, alkyl, cycloalkyl, or heterocyclicR’ = 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.
CH C
H
5
C
6
R
O
O
CH
2
CH
2
N(R')
2
CH
CH
2
OH
C N CH
2
H
5
C
2
N
OKratika Daniel (Ph.D)

13. 8/30/2012 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.
Kratika Daniel (Ph.D)