This document discusses alkaloids, including their classification, isolation, structure, and biological functions. It focuses on the alkaloids morphine, nicotine, and atropine. Morphine is isolated from opium through an extraction process using hydrochloric acid and ether. It is a powerful narcotic analgesic but is highly addictive. Atropine is isolated from belladonna through extraction with sodium carbonate and precipitation. It is used as an antidote and as a pupil dilator. The document provides methods for isolating these important alkaloids.

1. UNIT 5
Alkaloids: Definition, classification based on their structure
and biological functions,
Isolation, structure and biological action of morphine,
nicotine & atropine. Chemical synthesis of nicotine and
atropine

2. Alkaloids are often classified on the basis of their chemical structure. For example, those alkaloids that contain a
ring system called indole are known as indole alkaloids. On this basis, the principal classes of alkaloids are the
pyrrolidines, pyridines, tropanes, pyrrolizidines, isoquinolines, indoles, quinolines, and the terpenoids
and steroids.
Alternatively, alkaloids can be classified according to the biological system in which they occur. For example, the
opium alkaloids occur in the opium poppy (Papaver somniferum). This dual classification system actually
produces little confusion because there is a rough correlation between the chemical types of alkaloids and their
biological distribution.
The medicinal properties of alkaloids are quite diverse. Morphine is a powerful narcotic used for the relief
of pain, though its addictive properties limit its usefulness. Codeine, the methyl ether derivative of morphine
found in the opium poppy, is an excellent analgesic that is relatively nonaddictive. Certain alkaloids act
as cardiac or respiratory stimulants. Quinidine, which is obtained from plants of the genus Cinchona, is used to
treat arrhythmias, or irregular rhythms of the heartbeat. Many alkaloids affect respiration, but in a complicated
manner such that severe respiratory depression may follow stimulation. The drug lobeline (from Lobelia inflata)
is safer in this respect and is therefore clinically useful. Ergonovine (from the fungus Claviceps purpurea)
and ephedrine (from Ephedra species) act as blood-vessel constrictors. Ergonovine is used to reduce
uterine hemorrhage after childbirth, and ephedrine is used to relieve the discomfort of common
colds, sinusitis, hay fever, and bronchial asthma.

3. Contd: Medicinal properties of Alkaloids
Many alkaloids possess local anesthetic properties, though clinically they
are seldom used for this purpose. Cocaine (from Erythroxylum coca) is a
very potent local anesthetic.
Quinine (from Cinchona species) is a powerful antimalarial agent that was
formerly the drug of choice for treating that disease, though it has been
largely replaced by less toxic and more effective synthetic drugs.
The alkaloid tubocurarine is the active ingredient in the South American
arrow poison, curare (obtained from Chondrodendron tomentosum), and
is used as a muscle relaxant in surgery.
Two alkaloids, vincristine and vinblastine (from Catharanthus roseus,
formerly Vinca rosea), are widely used as chemotherapeutic agents in the
treatment of many types of cancer.

28. Morphine
OPIUM
12 % MORPHINE
Lone pair of
electrons on the
nitrogen atom
though, which is
what makes it an
alkaloid.

29. Isolating morphine from opium
The following is very useful to yield the morphine from opium.
1. Make up an 1 N solution of hydrochloric acid (HCl). [For 50 ml made of 25 % HCl you do the following: - Take 6.54
ml HCl (7.32 g) - Add them to 20 ml H2O - fill up to 50 ml with H2O ]
2. Dissolve 5 g Opium in 35 - 50 ml of 1 N Hcl.
3. Pour it into a sep-funnel.
4. Add 30 ml Ether to that.
5. Shake it powerful.
6. Seperate the layers. Keep the water layer. Discard the ether layer.
7. Pour the water layer back into the sep-funnel and repeat the shaking with ether.
8. Seperate the layers. Keep the water layer.
9. Make the aqueous solution pH 7 with sodiumhydroxide (NaOH). Morphine will precipitate out. Filter that out.
Here is what happens: The HCl makes everything that is available a salt. This is very soluble in water. When shaken
with ether, the ether takes everything else, but not the hydrochlorides which will stay in the water layer.
When the pH is neutralized, the morphine hydrochloride becomes a freebase again. This is not soluble in water and
so it precipitates out.
You might try to raise the pH with a carbonate instead of the hydroxide. Hydroxide might preform chemical reactions
and decompensate the morphine.

30. morphine, narcotic analgesic drug used in medicine in the form of its hydrochloride, sulfate, acetate, and tartrate
salts. Morphine was isolated from opium by the German chemist F.W.A. Sertürner in about 1804. In its power to
reduce the level of physical distress, morphine is among the most important naturally occurring compounds, being
of use in the treatment of pain caused by cancer and in cases where other analgesics have failed. It also has a
calming effect that protects the system against exhaustion in traumatic shock, internal hemorrhage, congestive
heart failure, and debilitated conditions (as certain forms of typhoid fever). It is most frequently administered by
injection to ensure rapid action, but it is also effective when given orally.
Morphine produces a relaxed, drowsy state and many side effects that result from the depression of the respiratory,
circulatory, and gastrointestinal systems. It also is an emetic and a general depressant. The most serious drawback
to the drug is its addictiveness.
Morphine is extracted from the dried milky exudate of the unripe seed capsule of the opium poppy (Papaver
somniferum). It occurs as colourless crystals or a white crystalline powder.

31. BIOLOGICAL SIGNIFICANCE OF MORPHINE
Morphine is a pain relieving medicine. It effectively alleviates moderate to severe pain.
Morphine is highly addictive and its use is associated with significant physical and psychological dependence. Some
of the major uses of morphine in clinical practice include: Relief of pain caused by heart attack or myocardial
infarction
Its duration of analgesia is about three to seven hours. Side-effects of nausea and constipation are rarely severe
enough to warrant stopping treatment.
It is used for pain due to myocardial infarction and for labor pains.

32. Isolation of Atropine
The herb of belladonna consists of dried leaves of Atropa
belladonna Linn. Mainly, it is cultivated in England, European
countries, India (Himachal Pradesh, Kashmir). For the cultivation it
needs an altitude of 1400 m above the sea level. The chemical
constituents of the drug includes 1% alkaloid, l-hyoscyamine.
Atropine is the racemate form of l-form and d-form of
hyoscyamine.

33. PROCEDURE
Isolation of atropine
From the juice of the powdered form of drug, atropine is isolated. By using the aqueous solution of Na2CO3, the
powdered drug material is thoroughly moistened and extracted by using ether and benzene. From the solvent, the
free base of alkaloid is extracted with acetic acid. To remove the colouring matter the acid solution is shaken with
ether and precipitation of alkaloid is carried out by using Na2CO3. Then the solution is filtered, washed and dried.
Again the dried sample is dissolved in acetone or ether and dehydrated by using anhydrous sodium sulphate before
filtration. A crude crystal of atropine is obtained after the concentration of filtrate following cooling of the solution.
For the complete racemization of hyoscyamine to atropine, we have to dissolve the crude crystalline sample in
alcohol and NaOH solution.
Detection of atropine
The sample solution is diluted and treated with concentrated HNO3. Evaporation of the mixture takes place for the
drying of sample on the water bath and it produce a pale yellow colour residue. A drop of freshly prepared KOH is
added to the yellow colour residue and the colour changes the violet (Vitali-Morin reaction)
Biological significance
The active constituent atropine was isolated and detected from belladonna plant. It is used as antidote for
anticholinesterase inhibitor toxicity, treatment of bradysystolic cardiac arrest, pupil dilator and other treatments.