Medicinal substances from a group of alkaloids

Alkaloids are biologically active organic substances of natural origin, which contain in
structure an atom (atoms) of nitrogen and have basic properties.
Alkaloids, according to their chemical structure are derivatives of various heterocyclic
compounds with heteroatom of nitrogen; they belong to tertiary amines.
Plants are the source of typical alkaloids and are basic, contain one or more nitrogen
atoms (usually in a heterocyclic ring), and they usually have a marked physiological action
on human or animals.
Physical properties
Alkaloids are solid crystalline substances, colourless, odourless, with a bitter taste.
Some alkaloids in the base form are fluids and have an unpleasant odour (colchicine,
nicotine, and physostigmine).
Most of the alkaloids are optically active. Alkaloids-bases are slightly soluble or
practically insoluble in water and freely soluble in various organic solvents (ethanol, ether,
benzene).
Salts of alkaloids, as a rule, are soluble in water and slightly soluble in organic
solvents. The exception is ethanol, which dissolves many salts of alkaloids. However,
bases of caffeine, ephedrine and pilocarpine are very soluble in water; some salts (cocaine
hydrochloride) are soluble in chloroform.
Knowledge of the solubility of alkaloids and their salts is of considerable
pharmaceutical importance. Not only alkaloidal substances are often administered in
solution, but also the differences in solubility between alkaloids and their salts provide
methods for the isolation from the plant and their separation from the nonalkaloidal
substances.
Tests of alkaloids
For identification of alkaloids are usually used general, group and specific reactions.
Most alkaloids are precipitated from a neutral or slightly acid solution by some reagents,
which according to the specificity of reaction are named precipitative reagents.
General precipitative reagents:
1. The solution of iodine in potassium iodide (Wagner reagent).
2. The solution of potassium bismuth iodide (Dragendorff reagent).
3. Potassium mercury-iodide solution (Mayer reagent).
4. The solution of cadmium iodide in potassium iodide (Marme reagent).
5. Phospho-molybdic acid (Sonnenschein reagent H3PO4.12MoO3.2H2O) – very
sensitive reagent for alkaloids; it gives amorphous precipitates with yellowish colour,
which in time become blue or green (reducing of molybdic acid).
6. Phospho-tungstic acid (Schebler reagent H3 PO4.12WoO3.2H2O).
7. Silico-tungstic acid (Bertran reagent SiO2.12WoO3.4H2O).
8. 5% tannin solution.
9. A saturated solution of picric acid (Hager reagent).
Reagents mentioned above, do not give precipitates with all alkaloids. It is necessary
to carry out the reaction at least with 4-5 reagents.
Only the negative result has analytical importance, as the reagents also give
precipitates with proteins and some other nitrogen-containing substances.
 Colour tests
1. Concentrated sulphuric acid.
2. Concentrated nitric acid.
3. The mixture of concentrated nitric and concentrated sulphuric acids (Erdmann
reagent).
4. A solution of ammonia molybdate in concentrated sulphuric acid (Frede reagent).
5. A solution of formaldehyde in concentrated sulphuric acid (Marquis reagent).
6. A solution of p-dimethylaminobenzaldehyde in concentrated sulphuric acid
(Wazicki reagent).
Classification
1. Derivatives of quinolisine (1) and quinolizidine (nor-lupinane) (2) (sparteine,
cytisine):

N N

2. Derivatives of tropine (atropine, hyosciamine, cocaine):

N C H3

3. Derivatives of quinoline (quinine) (1) and isoquinoline (opium alkaloids) (2):

N
N

1 2
4. Derivatives of imidazole (pilocarpine):

H N N

5. Derivatives of indole (physostigmine, strychnine, ergot alkaloids):

N
H

6. Derivatives of purine (caffeine, theobromine, theophylline):

N N H

N N

7. Derivatives of pyrrolizidine (platiphylline):

C H3

N
 Quinine and quinolizidine (nor-lupine) alkaloids
Cytisine (Cytisinum)

NH
N

They are derivative of 1,2,3,4-tetrahydro quinolizine-6, which is condensed with

piperidine.
Properties
White or slightly yellowish crystalline powder; freely soluble in water, alcohol and
chloroform.
Identification
1. Melting point 154-157оС.
2. Specific optical rotation: from 120о to 123о (for 2% aqueous solution).
3. Nitration of aromatic ring with the further reducing nitro-group to amino-group and
obtaining azo-dye.
4. With Co(NO3)2 a bluish-green precipitate appears.
3. With the FeCl3 solution, a red colour appears; it is discharged by water addition.
4. Reactions with general precipitative reagents.
Assay Acidimetry. Titrate with hydrochloric acid using methyl red solution as an
indicator; s=1.
H
+
NH + HCl N H Cl
N
N
O
O

Usage Respiratory and blood circulation stimulant.

Storage In well-closed containers protected from light.

Pachycarpine hydroiodide (Pachycarpini hydroiodidum)

N
. HI
N

-Sparteine hydroiodide
Properties
White crystalline powder, freely soluble in chloroform, soluble in alcohol and water.
Identification
1. Specific optical rotation: +8,6о to +9,6о (in 7% alcohol solution).
2. Reactions of iodides.
3. Obtaining of the pachycarpine base, which is determined by:
а) the product of reaction with picric acid (melting point);
b) interaction with bromine and ammonia vapours – the pink colour is obtained.
 4. With alkaline sodium nitroprusside solution a reddish-brown crystalline precipitate
appeared dissolves in excess of hydrochloric acid.
5. Reactions with general precipitative reagents.
Assay
1. Non-aqueous titration in the medium of anhydrous acetic acid in the presence of
mercury acetate (II); s=1/2:
N СH3COOH
. HI + Hg(CH COO) + 4 HClO
2 3 2 4
N

H
+
N -
2 . 2ClO + HgI2+2CH3COOH
+ 4
N
H

2. Argentometry by HI; s=1.

3. Alkalimetry by HI; s=1.
4. Photocolorimetry.
Usage Stimulant of the myometrium.
Storage Protected from light.