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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5467_Библиотеки_им_академика_М_И_Перельмана.pdf
152
Pharmaceutical Chemistry of Natural Products
2. Quinolines
HCO
3
N
Quinine
H
CH
2
HC
2
HO
H
N
CH CH⫽
2
HCO
3
N
Quinidine
H
CH
2
HC
2
HO
H
N
CH CH⫽
2
H
N
Cinchonine
H
CH
2
HC
2
HO
H
N
CH CH⫽
2
N
Cinchonidine
H
CH
2
HC
2
HO
H
N
CH CH⫽
2
H
H
H
3. Isoquinolines
HCO
3
HCO
3
N
CH
2
OCH
3
OCH
3
Papaverine
Noscapine
N
OCH
3
O
O
HC
2
CH
3
H
HCO
3
O
C
O
HCO
3
Berberine chloride
N
⫹
O
O
Cl
⫺
OCH
3
OCH
3
H
Alkaloids
153
N
HCO
3
HCO
3
H
H
H
H
CH
3
HN
OCH
3
OCH
3
Emetine
N
HCO
3
HCO
3
H
H
H
H
CH
3
HN
OCH
3
OH
Cephaline
HC
3
N
⫹
CH
3
H
O
OHHCO
3
OH
HC
3
N
⫹
H
H
O
OCH
3
( )-Tubocurarine⫾
Galanthamine
HCO
3
O
N
CH
3
OH
4. Phenanthrenes
CH
3
N
OH
O
H
HO
Morphine
CH
3
N
H
OH
O
HCO
3
Thebaine
Codeine
HCO
3
OCH
3
O
H
N
CH
3
154
Pharmaceutical Chemistry of Natural Products
5. Indole alkaloids
Ergometrine
N
CH
3
NH
HNOCC
H
CH OH
2
HC
3
Lysergic acid
HOOC
N
CH
3
NH
N
HN
CONH
H
H
CH
3
CH
3
O
N
OH
O
H
N
O
CH
2
H
Ergotamine
R
1
N
R
2
CH
3
H
N
R
3
Physostigmine
R = CH NHCOO —
R = CH
R = CH
13
23
33
N
H
N
H
HCO
3
H
H
C
HCO
3
O
OCH
3
O
C
O
OCH
3
OCH
3
OCH
3
Reserpine
Alkaloids
155
H
N
N
H
H
H
C
O
HCO
3
OH
H
N
N
CH CH
23
OH
H
COOCH
3
N
Vinblastine R CH
Vincristine R CHO
⫺
⫺
3
Yohimbine
R
N
HCO
3
HO C
O
OCH
3
OCOCH
3
H
CH CH
23
H
N
R
1
R
2
O
N
O
Strychnine R = R = H
Brucine R = R = OCH
12
12 3
⫺
⫺
6. Pyrrole and pyrrolidines
N
CH
3
CH
2
C CH
3
O
Hygrine
N
+
Me
COO
⫺
Stachydrine
Me
7. Tropane alkaloids
NCH⭈
3
OCOCH
CH
65
CH OH
2
O
OCO CH⫺
Atropine
Hyoscine
NCH⭈
3
CH
65
CH OH
2
156
Pharmaceutical Chemistry of Natural Products
NCH⭈
3
OOC CH⭈
CH
65
CH OH
2
Hyoscyamine
R= CH
R’= C H CO (Benzoyl)
3
65
Cocaine
COOR
OR’
H
NCH⭈
3
8. Imidazole or glyoxalines
HC
3
O
O
HH
NCH
3
⭈
Pilocarpine
N
9. Purines
O
CH
3
HCN
3
⭈
C
N
O
N
NCH
3
⭈
H C.N
3
C
O
N
CH
3
N
O
NH
HN
C
O
N
CH
3
N
NCH
3
⭈
O
Caffeine
Theophylline Theobromine
10. Terpenoid alkaloids
OH
OCH
3
HC
3
OCH
3
OCOC H
65
OH
OCOCH
3
OCH
3
Aconitine
OCH
3
HC
2
HO
N
Alkaloids
157
11. Steroidal alkaloids
HC
3
CH
3
CH
3
HO
N
CH
3
Solanidine
Conessine
HC
3
HC
3
N
CH
3
CH
3
CH
3
N
Nonheterocyclic Alkaloids
HO
C
C
H
N
H
CH
3
H
HC
3
OH
OH
CH
2
N
H
CH
3
HC
OH
( Adrenaline⫾)-Ephedrine
C
O
NH
OH
C
O
O
HC
3
H COCO
3
O
OH
CH
3
CH
3
CH
3
HO
AcO
O
CO
Taxol
O
158
Pharmaceutical Chemistry of Natural Products
MeO
MeO
OMe
NHCOCH
3
O
OMe
Colchicine
HO CH
2
CH
2
N
CH
3
CH
3
Hordenine
OCH
3
OCH
3
HCO
3
CH
2
CH
2
NH
2
H COOC
3
O
N( )⫹
N
()⫺
Serpentine
Mescaline
QUALITATIVE CHEMICAL TESTS FOR ALKALOIDS
General tests answered by all alkaloids are as follows:
1. Dragendorff’s test: To 2–3 mL of the alkaloid solution add few drops of Dragendorff’s reagent
(potassium bismuth iodide solution). An orange brown precipitate is formed.
2. Mayer’s test: To 2–3 mL of the alkaloid solution add few drops of Mayer’s reagent (potassium
mercuric iodide solution). White brown precipitate is formed.
3. Hager’s test: To 2–3 mL of the alkaloid solution add few drops of Hager’s reagent (saturated
solution of picric acid). Yellow precipitate is formed.
4. Wagner’s test: To 2–3 mL of the alkaloid solution add few drops of Wagner’s reagent (iodine–
potassium iodide solution). Reddish brown precipitate is formed.
5. For opium alkaloids: These alkaloids are present as salts of meconic acid. Opium is dissolved
in water, fi ltered and to the fi ltrate, ferric chloride solution is added by which deep reddish
purple colour is obtained. The colour persists even upon adding hydrochloric acid.
6. For tropane alkaloids ( Vitalis–Morin reaction): Tropane alkaloid is treated with fuming nitric acid,
followed by evaporation to dryness and addition of methanolic potassium hydroxide solution
to an acetone of nitrated residue. Violet colouration takes place because of the presence of
tropane derivative.
7. For purine alkaloids ( murexide colour reaction): Caffeine is taken in a Petri dish to which
hydrochloric acid and potassium chlorate are added and heated to dryness. A purple colour is
obtained by exposing the residue to vapour of dilute ammonia. The purple colour is lost upon
addition of alkali. Caffeine (and other purine alkaloids) gives murexide colour reaction.
Alkaloids
159
ISOLATION OR PRODUCTION OF ALKALOIDS
Alkaloid bearing plant usually contains a complex mixture of alkaloids, hence isolation and
purifi cation of an alkaloid from a plant is always not a simple process. Further, the presence of
organic acids, glycosides, etc., present in the plants may complicate the isolation process. Thus,
isolation of pure alkaloid may often become a laborious procedure.
The steps involved in the isolation of an alkaloid may be summarized as follows:
1. The presence of an alkaloid in a plant is ascertained by using the various alkaloidal reagents.
(Refer the qualitative tests mentioned above.)
2. The next step is the separation of relatively small amount of alkaloids from large amount of
extraneous plant materials.
3. The fi nal step is the separation and purifi cation of individual alkaloids from the crude
mixture.
The isolation of an alkaloid from the crude powdered drug is schematically represented below.
Powdered drug containing alkaloid salts (tannates, oxalates, etc.)
Free alkaloids
Total extract
1. Defat if necessary with petroleum ether
2. Moisten and render alkaline with Na
2
CO
3
or
K
2
CO
3
or NH
3
or Ca(OH)
2
Extract the alkaloid with organic solvent like CHCl
3
, ether
Concentrate and shake the extract with succes-
sive quantities of acid like dil. H
2
SO
4
Aqueous acid solution of alkaloid
Make alkaline with Na
2
CO
3
and extract alkaloids with an
immiscible solvent like CHCl
3
Fractional crystallization, fractional precipitation,
column chromatography, partition chromatography, gas
chromatography or by counter current extraction
Residual aqueous fraction
Crude alkaloid mixture
Individual alkaloids
Distil off the solvent
Organic solution of the alkaloid bases
Residual organic fraction
(Pigments, fats and occasionally very weak
bases or chloroform soluble alkaloid sulphates)
160
Pharmaceutical Chemistry of Natural Products
DETERMINATION OF MOLECULAR STRUCTURE OF ALKALOIDS:
GENERAL METHODS
As the molecular structure of alkaloids is complex, only recently few of the complex alkaloids’
structures were elucidated. The various chemical methods performed to determine the structure
of alkaloids is as follows:
Molecular Formula Determination
The fi rst step in structural elucidation is the determination of molecular formula and optical
rotatory power. Elemental composition and hence the empirical formula is found by combustion
analysis.
Hydrolysis
Simple fragmentation by hydrolysis with water, acid or alkali yields simple fragments which are
then analysed separately. For example, atropine on hydrolysis yields tropine and tropic acid.
Determination of Unsaturation
The unsaturation can be determined by adding bromine, halogen acids or by hydroxylation with
KMnO
4
or by reduction (using either LiAlH
4
or NaBH
4
).
Functional Group Determination
By using the usual standard chemical tests or by infrared (IR) spectroscopy, functional nature of
the alkaloids is determined.
Functional nature of oxygen: The oxygen atom may be present in the form of alcoholic hydroxyl
(–OH), phenolic hydroxyl (–OH), methoxyl (OCH
3
), acetoxy (–OCOH
3
), benzoxyl (–OCOC
6
H
5
),
carboxyl (–COOH), aldehyde (–CHO), ketone (C=O) and methylene dioxide group (–O–CH
2
–O–).
These groups are characterized by the chemical tests as follows:
Phenolic hydroxyl group (
=
C–OH)
It is identifi ed by the following tests:
Soluble in alkali and reprecipitation by CO
2
.
Violet colouration with neutral ferric chloride.
Yields ester on acetylation. This reaction can be used to determine the number of phenolic
–OH.
Yields ether on reaction with alkyl halide.
Alkaloids
161
Alcoholic hydroxyl group (–C–OH)
It yields ester on acetylation and benzoylation (but negative answer for phenolic –OH)—refer
above tests.
This is confi rmed by oxidation, dehydration, dehydrogenation and by spectroscopy (IR and
NMR). Alcohols are of three different types: 1°, 2° and 3°, and they are usually distinguished by
their oxidation products.
Primary alcohol
R—CH —OH
2
(O)
R—CHO
(O)
R—COOH
Aldehyde with
same no. of
‘C’ as in alcohol
Carboxylic acid
with same no. of
‘C’ as in alcohol and
aldehyde
Secondary alcohol
R—CH CH CH
23
——
OH
(O)
R—CH C CH
23
——
O
(O)
RCH COH
2
———
O
Ketone with
same no. of
'C' as in alcohol
Carboxylic acid
with fewer no. of
'C' with respect to
alcohol and ketone
But in cyclic structure, 2° alcohol yields different oxidation products as shown below:
OH O
COOH
COOH
Ketone with
same no. of
'C' as in alcohol
Acid with same no. of
'C' as in alcohol
(O) (O)
Tertiary alcohol
RCH CCH
23
———
OH
CH
3
(O)
RCH CCH
23
———
O
(O)
RCH COH
2
———
O
Ketone with
lesser no. of
'C' with respect to
alcohol
Carboxylic acid
with fewer no. of
'C' with respect to
alcohol and ketone