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The world over the total trade of medicinal plants about 8800-lakh
dollar, of which contribution of India in world trade less then 1%.
Out of this majority of plants are yet to be study photochemical, estimated of
such pants to the extent of 5000 to 6000.
1
This definition not fully correct because not follow on all alkaloids for
e.g.
Colchicine: Colchicine is regarded as an alkaloid although it is not
Heterocyclic and is scarcely basic.
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OCCURRENCE OF ALKALOIDS
They are present in the form of salts of organic acid, like acetic acid,
oxalic acid, malic, lactic, tartaric, tannic, aconitic acid, few are with sugar e.g.
Solanum, veratrum groups. Acc. to parts of plants:
Leaves: Nicotine
NOMENCLATURE
There was no systematic nomenclature. But there are some methods for
nomenclature are mention below.
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CLASSIFICATION
C) Bio Synthetic based: According to this alkaloids are classified on the basis
of the type precursors or building block compounds used by plants to
synthesise the complex structure. e.g.. Morphine, papaverine, narcotine,
tubocurarine & calchicine in phenylalanine tyrosin derived base.
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3) Pyridine & Piperidine: Alkaloids containing Pyridine Heterocyclic
ring in their structure e.g. Nicotine, Lobaline, Piperidine, Ricinine.
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I. Mayer (Cream Co lour) Test II. Marquis (Conc. HCHO) Test. III. Erdmann
(Conc. HNO3) Test IV. Hager's (Yellow Colour) Test V. Frohdes (Molybdic
acid) Test
2. Extraction: - The plants is dried, then finally powdered and extracted with
boiling methanol. The solvent is distilled off and the residue treated with
inorganic acids, when the bases (alkaloids) are extracted as their soluble salts.
The aqueous layer containing the salt of alkaloids and soluble plant impurities
is made basic with NaOH. The insoluble alkaloids are set free precipitate out.
The solid man (ppt.) so obtained is then extracted with ether when alkaloid
pass into solution and impurity left behind. Flow Chart of extraction
Basic Material
(Crude Alkaloids)
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3. Separation of Alkaloids: After detection of next step is separation of a
relatively small percentage of alkaloids from large amount of crude
drugs. E.g.- Opium contains 10% Morphine, Chincona contains 5-8 %
Quinine, Belladona- 0.2% of Hyoscyamine.
PHYSICAL-PROPERTY
IV) Optically active, Most of levo ratatory but few are -Dextro rotatory
e.g. Coniine, some inactive- e.g.- papaverine.
1. Mayer's Test: Specimen with Mayer's reagent give Cream or pale yellow
ppt.
4. Hager's Test: Specimen with Hager's reagent give yellow ppt. (Special
Type)
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GENERAL METHODS FOR STRUCTURE DETERMINATION OF
ALKALOIDS
If Primary amines are present in an alkaloids also give this test. Then
Hydroxyl group is can be determined by zerewitinoff method.
NaOH
R-OH +CH3COCl R-OCOCH3- R- OH +CH3COONa
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- OH + MeMgI - OMgI + CH4
- NH + MeMgI - NMgI + CH4
HI AgNO3
C2OH4OO4N 4MeI 4AgI (estimated gravimetrically)
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b) Ester Amide Lacton & Lactum group: These groups are identified
by the estimation of product.
Heat
>CONH2 + NaOH -COONa + NH3
Heat
>COOR + NaOH -COONa + ROH
c) Nature of Nitrogen
Majority of nitrogen presence in alkaloids are secondary and tertiary: If
tertiary when treated with H2 O2 (50%) form.
=N +H2O2 =N O +H2O
N-methyl group:
On distillation with soda lime if methylamine is produce show the
presence of N-methyl group for e.g.
Soda-lime
(C10H14N)=N-CH3 CH3NH2
Nicotine CaO
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N- methylamine + HI 1500-3000 >NH + MeI AgNO3
AgI
Estimated gravimetrically
K2Cr2O7 or H2SO4
-C-Me MeCOOH
Estimated gravimetrically
e) Degradation of Alkaloids: For discovering the structural system which
incorporate these substituents groups & is tackled by degradation of the
molecules by following methods:
1) Hoffmann's exhaustive methylation: - This is a composite reaction
of alkaloid (Heterocyclic amines). This involves following steps:
c) The step Ist and IInd are repeated when a second cleavage at the N-atom
given an unsaturated hydrocarbon which isomerase’s to conjugated derivative.
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The exhaustive methylation of an alkaloid is an important method for the
investigation of the nature of the C-skeleton in the heterocyclic system.
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NaOH Br2 Distillation
R2NH+ C6H5COCl R2N-COC6H5 R2NCBr2C6H5 Br-RRBr + C6H5CN
K2Cr2O7 (H2SO4)
C10 H14N2 C6H5COOH
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BIOSYNTHESIS OF ALKALOIDS
vii Trytophen
PHYSICAL METHOD
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These following physical methods are applied to elucidate the structure
of alkaloids:
• U.V. Spectroscopy
• IR Spectroscopy
• Nuclear Magnetic resonance spectroscopy
• Mass spectroscopy
• Optical rotatory dispersion & circular dichroism.
• Conformational Analysis
• X-Ray diffraction
1. ATROPINE
This is the most important alkaloid of tropane group and occurs in the
roots of deadly nightshade (Atropa belladonna), thron apple (Datura
stamonium)n and many other member of solanaceous family together with l-
hyoscyamine which is optically active ( [<]D = -220 ). Atropine is the racemic
form of l-hyoscyamine which readily racemises to atropine when warmed in
an ethanolic alkaline solution, thus atropine is
( ± )-hyoscyamine
ISOLATION
STRUCTURAL ELUCIDATION
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UV ( Ethanol ): λmax 246, 251.6, 257, 263.5, 271 nm ( c 147.6, 175.1, 209.8,
143.3 and 24.6 respectively )
2. MORPHINE
ISOLATION
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(i) First of all, the raw opium is extracted with cold dichloromethane
repeatedly. Papaverine, narcotine and gum go into the dichloromethane layer
whereas morphine and other substances remain in the insoluble residue.
Dichloromethane layer is separated.
(ii) The dichloromethane layer obtained from step (i) is evaporated to
dryness to yield a residue which is extracted with hot dilute HCl, then treated
with the charcoal and finally filtered. The filtrate is neutralized with ammonia
when papaverine and narcotine are precipitated out. When precipitate is
shaken with hot alcohol, the papaverine goes into alcohol. From this,
papaverine is precipitated out as oxalate and then purified by recrystallisation.
The crude narcotine present in the residue from the alcohol extraction is
similarly purified.
(iii) The residue obtained from the dichloromethane extraction is
agitated with lime water at temperature below 20oC. morphine, codeine and
thebaine are present in lime water which when extracted several times with
benzene remove codeine and thebaine in a benzene layer. Then, the pH is
raised to 8 when the crude morphine is precipitated out. The filtrate still
contains morphine. This filtrate, when evaporated in vacuum and then
extracted with amyl alcohol, yields further amount of crude morphine. the two
sample of crude morphine are mixed.
(iv) The crude morphine obtained from step (iii) is dissolved in dilute
HCl and filtered through alcohol. Then the filtrate is neutralized with
ammonia followed by the addition of alcohol. This results in precipitation of
morphine. The precipitated morphine is dissolved in minimum quantity of
dilute HCl and the resulting solution so obtained on concentration and cooling
yields crystals of morphine hydrochloride.
(v) The benzene extract obtained from step (iii) is evaporated to yield a
residue. This is then treated with hot alcohol, followed by cooling and
filtration. The filtrate when treated with sulphuric acid yields a precipitate of
codeine sulphate which is filtered out. To the resultant filtrate, tartaric acid is
added to precipitate out thebaine as thebaine acid tartrate.
STRUCTURAL ELUCIDATION
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UV ( Ethanol ): λmax 286, 250 and 298 nm ( log c 3.256, 3.275, 3.360
respectively )
3. EPHEDRINE
ISOLATION
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1 kilo of powdered Ma Huang was extracted with cold benzene in the
presence of dilute Na2CO3 solution, and the benzene extract was shaken up
with a sufficient quantity of dilute HCl to remove the basic substances. The
acid solution was made alkaline with solid K2CO3 and the liberated base was
then extracted with chloroform. The chloroform solution, when dried over
anhydrous Na2SO4 and distilled, gave 2.6 g of crude base.
The crude base obtained as above was taken up with about twice its
weight of alcohol and neutralized with concentrated HCl diluted with twice its
volume of alcohol. Nearly pure ephedrine hydrochloride crystallized out on
standing. After filtering it was washed with a mixture of alcohol and ether, and
then with pure ether, and dried. A further quantity of ephedrine hydrochloride
may be got by concentrating the mother liquors and washings. The final
mother liquor was kept for the isolation of pseudoephedrine (see below).
STRUCTURAL ELUCIDATION
UV (Methanol): λmax 250, 256 and 262 nm (log c 170, 20, 165 respectively)
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4. RESERPINE
ISOLATION
Mature root bark (264 g) was extracted with methanol in a Soxhlet for
30 hr, the extract concentrated to remove the methanol, and the residue treated
with NaHCO, solution and ether. Any resinous material separating at this stage
was dissolved in a little methanol and retreated in the same way, this process
being repeated thrice or until no more resin formation occurred. All the
aqueous solutions were extracted four times with ether and the combined ether
extracts washed with 2% acetic acid (3~100c.c.) then 2% HC1 (2 x 100 c.0.).
The combined acid extracts were then Basification with NH, gave a resin
which would not dissolve in ether. A solution of this material in a little
methanol gradually deposited a crystalline precipitate which after several
recrystallizations from methanol (Yield 0.07 g). A further quantity was
obtained on longer standing.
STRUCTURAL ELUCIDATION
Structure-
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UV: λmax 296, 267, 216 nm (c 9660, 15700 and 55700 respectively )
IR: Vmax 3480 ( N-H stretching ), 2840-3030 ( C-H stretching ), 1732 and 1713
( C=O stretching ) cm-1.
1
H-NMR (CDCl3 ): δ 7.85 ( s, NH ), 6.7-7.3 ( indole Ar-H ), 7.34 ( 2H, s,
trimethoxybenzene Ar-H ), 5.05 ( H-18, m ), 4.43 ( H-3, t ), 3.92 ( 6H, s,OMe
X 2 ), 3.29 ( 3H, s, CH-OMe ), 3.79 ( 3H, s, C16- OMe ), 3.46 ( s, C17 OMe )
5. VINCRISTINE
ISOLATION
The mixture of dried ground plant of Vinca rosea and dilute tartaric acid
is extracted with benzene. Collect benzene extract and evaporate till
concentrate. The concentrated extract is then steam distillated to obtain
insoluble residue. Dissolve the residue by mixing it with dilute tartaric acid
and hot methanol, and then distill out the methanol from it .Carryout the
extraction of the bottom product using dilute solution of ammonia. Collect the
extract, evaporate and dry. The dried powder of Vincristine is dissolved in
benzene and chromatographic separation is carried out on alumina column
using eluting solvents as benzene, benzene + Chloroform, Chloroform and
Chloroform + Methanol mixture.
STRUCTURAL ELUCIDATION
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UV: λmax 296, 290, 275, 255, 221 nm (c 15600, 14000, 11400, 15400 and
47100 respectively ).
MS : m/z 824 ( M +, negligible ), 806 ( M+ - 18 ).
Functions
Alkaloids functions -
• As reservoir of nitrogen
• As reservoir for protein synthesis
• As detoxicating agents
• As toxicating agents
• As harm one for many activity of plant.
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Alkaloids have many physiologically biological and pharmacological
properties
Conclusion
It can be concluded that:
1. Alkaloids are naturally occurring heterocyclic complex compounds.
2. Alkaloids have indefinite definition.
3. Alkaloids have mainly nitrogen in heteroatom.
4. Alkaloids have complex molecular structure.
5. Alkaloids are bio & physiologically and pharmacologically active.
Reference:
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4) Gupta A.K. Vol-1, Quality Standards of Indian Medicinal Plants,
ICMR, New Delhi.
5) Evans W.C., (Fifteenth edition) Trees & Evans Pharmacognosy,
W.B. Saunders.
6) Agarwal. O. P., Vol-2, Chemistry of Natural Product, Goel
Publication Meerut. Page 193-311.
7) Finar I. L., Vol-II Vth edition, Organic Chemistry (Stereo-
chemistry & Chemistry of Natural Products) ELBS. , Page 696-
702
8) Robert MF, M Wink, Alkaloids (Biochemistry, Ecology,
Medicine application) Plenum Press, N. York.
9) Brunton Jean, 2nd edition, Pharmacognosy Phytochemistry of
Medicinal Plants, Levoisier Paris. Page 783-799.
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