1. Atropine occurs in Atropa belladonna together with hyoscy-amine.
Source
The alkaloid atropine mainly present in Atropa belladonna and also in Datura stramonium.
Atropine occurs in Atropa belladonna together with hyoscy-amine.
Hyosci-amine is typically active [α]D -22 °C but readily recemizes to atropine.
When warmed in an ethanolic alkaline solution.
Chemistry
Its molecular formula is C17H23NO3. ­Its melting point = 118 °C.
It is the recemic mixture of d & l hyoscy-amine.
Atropine itself is more stable than either of d & l isomer and is usually preferred.
It is an organic ester formed by the combination of aromatic acid,
tropic acid and an organic base troppine.
Structure
Its molecular formula is C17H23NO3
IDH = C17H17× = C17H37
IHD = 37 – = 14/2 = 7 2

2. Atropine No reaction Atropine No reaction Tropic acid + Tropine
Hydrogenation
When atropine was subjected to catalytic hydrogenation, no mole of molecular hydrogen was consumed. It means that the molecule does not contain C=C bond.
Atropine
No reaction
Bromination
Bromination also proved that the compound is not unsaturated and does not contain C=C bond.
Atropine
No reaction
Hydrolysis
When warmed with Ba(OH)2 atropine is hydrolyzed to (±) tropic acid and tropine. Thus atropine is tropine ester of tropic acid
Tropic acid + Tropine
Atropine
(±)
(±)

3. The molecular formula of tropic acid is C9H10O3.
Melting point = 117 °C. Its optical activity is
[α ] ± 81.5°
IDH = C9H9× = C9H20
IHD = 20 – = 10/2 = 7 2
Hydrogenation
On catalytic hydrogenation no mole of hydrogen is
consumed so it is a saturated compound.
Bromination
Bromine does not add to the tropic acid.
It also shows that tropic acid is a saturated compound.
Nature of Oxygen
Esterification
On treatment with an alcohol tropic acid gives an ester. It means that one carboxylic group is present in tropic acid.
Decarboxylation
When tropic acid is strongly heated CO2 is evolved. This also confirms the presence of a carboxylic acid group.
Thus two oxygen atoms are present in the form of COOH group.
Esterification:
On treatment with carboxylic acid an ester is obtained. It means that the tropic acid also contain a hydroxyl group.

4. This structure is further supported by the fact that the oxidation of
On controlled oxidation an α aldehyde carboxylic acid is formed which on further oxidation is converted into dicarboxylic acid.
This result shows that the alcoholic group is present in the form of primary alcohol which is oxidized to an aldehyde and
further oxidation gives dicarboxylic acid. Thus the structure of tropic acid can be
Dehydration
When heated strongly tropic acid loses a molecule of H2O to form atropic acid (C9H8O2) .
This shows that both trpic and atropic acids contain benzene ring with one side chain.
Thus the structure of tropic acid is either 1 or 2.
But since 1 is called cinnamic acid. So the structure of atropic acid is 2.
This structure is further supported by the fact that the oxidation of
atropic acid gives phenyl glyoxylic acid.
Addition of H2O molecule to atropic acid gives tropic acid which may
have any one of the following 2. Structure 3 & 4.

5. Pharmacological Action
Synthesis of tropic acid
Synthesis of tropic acid has shown that the real structure of tropic acid is 4. The starting material is acetophenone.
This synthesis gives ± tropic acid which has been resolved by means of quinine.
Pharmacological Action
Atropine dilates the pupil of eye by relaxing circular fibers of the iris.
This effect is called mydriasis.
Gastro Intestinal Tract
Atropine markedly reduces the secretion of saliva.
The mouth becomes dry and swallowing and talking becomes difficult.
Gall bladder
Atropine has a mild antispasmodic action on the gall bladder and bile ducts.
Urinary tract
Atropine decreases the normal tone and amplitude of the ureter and urinary bladder.

6. Respiratory tract
Atropine reduces the secretion of the respiratory tract
Medicinal and therapeutic uses
Excessive salivation
Atropine is used in reducing excess in salivation associated
with parkinsonism and heavy metal poisoning.
Peptic ulcer
Atropine reduces the secretion of gastric acid and thus prevents peptic ulcer
Nocturnal Enuresis
Atropine is used for the treatment of nocturnal enuresis in children.
Motion sickness
It is an effective agency for motion sickness
During short duration journey Parkinsonism
It is also used Parkinsonism diseases
Hyperhidrosis
Atropine may be used in the treatment of rare cases of hyperhidrosis.
Mushroom poisoning
It is a specific antidote for the rapid type of mushroom poisoning.
Antidiarroeal
Intestinal hyper motility and increased frequency of stools are well controlled by an atropine.
Respiratory abstruct diseases
It is quite effective in chronic bronchitis which causes obstruction of the air way.
Antispasmodic
Atropine has been used for the treatment of intestinal, billary and renal colics.
It is also used half an hour before general anaecthesia.

7. Quinine
Molecular Formula is C20H34N2O2

8. Quinine It is alkaloid isolated from the bark of cinchona tree.
Quinine is the oldest of all therapeutic agents used in the treatment of malaria.
It is still a useful agent in the treatment of cerebral malaria.
Chemistry
Its molecular formula is C20H34N2O2. Melting point = 177 °C.
IDH = C20H20 × = C20H42
IDH = = 20/2 = 10 2 .

9. Nature of Nitrogen
Quinine adds 2 moles of CH3I to form a diquaternary salt. Therefore it is ditertiary base
Hydrogenation
On catalytic hydrogenation one molecule of hydrogen is added to quinine thus it contain one C=C bond.

10. On bromination quinine adds one molecule of bromine.
Thus it proves the presence of one C=C bond.
Reaction with HCl
When heated with HCl quinine eliminates one carbon atom as CH3Cl.
This indicates about the presence of a methyl group in the molecule

11. Nature of oxygen
Since quinine forms mono acetate and mono benzoate,
one hydroxyl group must be present.
Oxidation Oxidation of quinine with CrO3 produces quinine (ketone),
therefore the nature of the hydroxyl group is a secondary alcohol.

12. Oxidation of quinine with CrO3 produces among other products quininic acid.
This shows that quinine contain the following nucleus
(Quinoline nucleus) with branching at the labeled position.

13. Let us elucidate the structure of quininic acid.
Oxidation of quinoline with KMnO4 gives HCOOH along with the other oxidation products.
This indicates the presence of terminal C=C bond.
Fro the above facts it is clear that the second half of the structure of quinine is similar to that of cinchonine.
Let us elucidate the structure of quininic acid.
When heated with soda lime quininic acid undergoes decarboxylation
to give a methoxy quinnoline.
OCH3 may be present at any position

14. On oxidation with CrO3 quininic acid give pyridine 2, 3, 4 tricarboxylic acid.
This reaction indicates OCH3 group is present in benzene ring.
The position of OCH3 group was indicates by heating quininic acid with HCl
and decarboxylating the methylated product 6-hydroxy quinoline was obtained.
It means quininic acid is methoxy cinchonininc acid.
Synthesis of quininic acid
The further support to this structure of quinoninic acid was provided by its synthesis.
The synthesis of quininic acidnis

15. Biosynthesis of quinine

16. Ephedrine Botanical source and previous history:
Ephedrine is an alkaloid which can be obtained from the stems of various species of Ephedra.
It is one of the most important of drug in Mahuang.
The drug Mahuang containing Ephedrine was known to Chinese in 2800 B.
It was introduced to the western medicine in The pure alkaloid obtained was named by Nagi.
It was 1st synthesized in Chen and Schnidt investigated its pharmacology
and this led to wide interest in its use as a medicinal agents.

17. Pharmacological Action:
Pharmacological action of ephedrine is given below.
It has been used in the treatment of hay fever bronchial asthma etc.

18. Cardiovascular effect:
These effects are similar to that of ephedrine in many ways.
The drug elevates the systolic and diastolic pressure in man and pulse pressure increase.
The heart rate may not be altered but it increases if vagal reflexes are blocked.
The force of myocardial contraction and cardiac out put are increased by the drug.
Cerebral coronary and muscle blood flow are increased by drug
Bronchial Muscles:Relaxation is less prominent more sustainable with ephedrine.
Thus ephedrine is of value in milder cases of a cute asthma.

19. Myorialsis occurs after the local application of the drug to the eye.
The smooth muscles are affected in the same manner as by ephedrine.
The activity of human uterus is reduced by the medicine.
Therefore, this medicine is used to relieve the pain of dysmenorhea.
It is less effective than ephedrine in elevating the concentration of blood sugar.
The CNS effects of ephedrine are less marked.
It is effective for asthma, hay fever low blood pressure urticaria, muscle weakness etc.

20. IHD C10H15NO or C11H16
C11H11 × = C11H24 = 24 –16/ = 8/2 = 4

21. Nature of Nitrogen
On exhaustive methylation two molecules of CH3-I are used.
CH3-I

22. Structural Elucidation
The molecular formula of ephedrine is C10H15NO.
On oxidation ephedrine forms benzoic acid.
This shows Ephedrine contain a benzene ring with only one side chain.

23. Structure of Ephedrine (Stereochemistry):
Ephedrine has two asymmetric carbon atoms thus there are four optically active forms.
According to Reundberg the configuration of ephedrine and Ψ ephedrine are given below

24. Bromination Hydrogenation
When ephedrine is subjected to hydrogenation. No hydrogen molecule was consumed it mean that ephedrine is saturated compound.
On bromination no bromine molecule are consumed it mean that ephedrine is saturated and don’t contain C=C.
Bromination

25. Nature of Oxygen
When heated with HCl it gives methyl amine and propion phenone as
CH3-NH2 + C6H15COCH2CH3
The formation of these two product indicates that the structure of ephedrine 1 or 2.
C6H5-CH-CH2-CH2-NH-CH3 C6H5-CH(OH)-CHN(CH3)-CH3

26. It has been observed that the structure 2 undergoes the Hydramine fission to form propiophenone when heated with HCl. Thus 2 is more likely than 1.
This is supposed by the fact that when ephedrine is subjected to Hoffman exhaustive methylation method to give 1,2 methyl phenyl oxide 3.
This can be supported 2 but not by 1.

27. Further support for the structure 2 is provided by following evidence
structure 1 contain one chiral centre
C6H5-CH(OH)-CH2-CH2-NH-CH3 and so the replacement of the hydroxyl group by hydrogen will result in the formation of an optically inactive compound.

28. Nagai synthesis

29. Structure 2 contains two chiral centers and so the replacement of the hydroxyl group by hydrogen should still give a compound which is optically active observed experimentally it has been observed that when this replacement is carried out in (-) ephedrine. The product deoxyephedrine in optically active. Thus the structure 2 agrees all the known facts. This structure has been confirmed by the synthesis carried out by Nagai.

30. Stereochemistry
Ephedrine has 2 asymmetric carbon atoms. Thus there are four optically active forms. According to the Frend berg
The configuration of ephedrine and Ψ ephedrine are given below.

31. Physiological Action
Physiologically its action is similar to that of adrenaline.
It can be taken orally. It has been used in the treatment
of hay fever and Broncchial asthma etc.
Ephedrine stimulates epinepherine in physiological effects
but its pressure action and val constrictor action are of greater duration.
It gives more pronounced stimulation of CNS than does epinephrine.
It is effective when given orally or systematically.
Ephedrine and its salts are used orally intravenously and intramuscularly and topically in a variety of conditions such as allergenic disorder colds hypoten sive condition and norcolepsy

32. Colchicine Introduction It occurs in the seeds of corns. ]
The plants belonging to the family lilliaceae.
It has been used for the treatment of diagnosis of gout.
In 1932 it was discovered that it can arrest cell division at a parcular cell.
Therefore it was used for the arterial production of polypoid varieties of numerous plants.
It melting point in the form of needle is °C. It’s a base and is soluble in H2SO4.

33. Molecular formula = C22H25O6N Presence of enol methyl ether group
Structure and Reaction
Molecular formula = C22H25O6N
Presence of enol methyl ether group
When colchicine is hydrolyzed with dilute acids it yields
a mixture of an acid substance called colchicein C21H23O6N and CH3OH.
This reaction reveals the presence of enol methyl ether group in colchicines.
C22H25O6N + H2O
C21H23O6N + CH3OH

34. Presence of acatamide group
When hydrolyzed with strong acids colchicine yields acetic acid and a new base called trimethyl colchicinic acid C19H21O5N.
This reaction clearly indicates the presence of an acetamide group NHCOCH3.
C21H23O6N + H2O
C19H21O5N + CH3CO2H
Trimethyl colchicine
NH-CO-CH3 + H2O
NH2 + CH3COH

35. When trimethyl colchicinic acid is further subjected to hydrolysis under vigorous conditions, it yields one mole of colchicinic acid and 3 mole of methyl halide.
This indicates the presence of 3 mehtyl groups in trimethyl colchicinic acid and colchicines.

36. The above reaction indicate the nature of five oxygen atoms
which are present in the form of
3, oxygen atoms are present in 3-OCH3 group
1, oxygen atoms are present in –N-COCH3 group
1, oxygen atoms are present in ether group
The sixth oxygen atom has been found to be present as
unreactive carbonyl group.
Thus colchicine may be represented as
4-OCH3
1-C=O
1-NH-CO-CH3 group
Tricyclic nature of colchicine:
Catalytic hydrogenation gives hexahydro colchicine.
In this reaction 2 C=C bonds and one C=O group.
Epoxidation
Epoxidation of the above reduced product gives an epoxide.
This indicates that hexahydro colchicine still contains an isolated C=C bond.
Thus colchicine must contain 3C=C bond.

37. Oxidation Nature of ring B
When colchicine is treated with KI, it yields N-acetyl iodide colchinol.
Oxidation
Oxidation of colchicine and its derivatives yields 3,4,5 trimethoxy pthalic acid.
This indicates the presence of a benzonoid nucleolus in colchicines
Colchicines (C22H25O6N)

38. Thus the fully reduced hydrocarbon would posses the composition C16H28 and saturated hydrocarbon follows the general formula CnH2n-4 for tricyclic compound.
Let us consider that 3 rings present in colchicine are A, B, and C. Let us establish the nature of these rings one by one.
Nature of ring A:
As mentioned above, the oxidation of colchicine gives 3,4,5 trimethyl pthalic acid. This indicates
the nature of ring A as well as the position of 3-OCH3 group.
Colchicine

39. Nature of ring B:
When colchicine is treated with KI, it yields N-acetyl iodide colchinol.
N-acetyl iodocochineal
Colchicine