Seminar on Alkaloids

Prem Kumar Malviya M.Pharma

ALKALOIDS
Alack, alack, is it not like that I, So early waking, what with loathsome smells, And shrieks like mandrakes' torn out of the earth That living mortals, hearing them, run mad. Romeo and Juliet ; Act IV, Scene 3

HISTORY
most notorious poisons in the history of civilization. used by humanity for thousands of years. The first civilizations to use them were probably the ancient Sumerians and Egyptians it was called a vegetable alkali.

Mandrake, also named Mandragora (Mandragora officinarum) Most magic plant.

The name alkaloid comes from the Arabic word for ash al-qali. Belladonna is also named Devils Cherries.
Term alkaloid was coined by meissner ,a German pharmacist (1819). Derosne (French chemist) isolated Narcotine (1803). . Serturner (1803) isolated morphine from opium

FACTS ABOUT MANDRAKE

Already used in Egypt 3500 years ago. Grecian times considered as an extremely powerful aphrodisiac and fertility enhancer. Mentioned in the Koran, and strictly forbidden. The sponge that was given to Jesus on the cross is said to contain Mandragora juice. played a major role in witchcraft. Witches prepared mixtures of extracts of henbane (Hyoscyamus niger), deadly nightshade (Atropa belladonna) and mandrake root, to be applied on the skin or on the genitals.

DEFINITION

???????
NO DEFINITE DEFINITION

naturally occurring nitrogenous substance which is isolated from plants and reacts like bases

Konigs (1880):- Naturally occurring organic bases which contains a Pyridine ring.

Ladenburg Alkaloid are natural plant compound that have basic character and contains at least one nitrogen atom in heterocyclic ring.

Again, this definition is not correct because

MUSCOPYRIDINE

Basic nitrogenous compound, contains one or more nitrogen in heterocyclic ring system having marked physiological action on human and animals when use in small quantities
.

MORPHINE

1. Analgesic action :- Morphine oral;-10-50mg , i.m :-1015mg , i.v. :-2-6 mg Pethidine i.m :-50-100mg Aspirin oral :--600mg Codeine oral :--60 mg.
2. Anti-cancer activity. Cytrabine (Pyrimidine antagonists) is an Anti-cancer drug (1.5-3.0 mg/kg i.v.). Vinblastine ( mitotic inhibitor) is an anti-cancer drug (0.1-0.15mg/kg i.v) Both of above drug are used in treatment of Hodgkins disease.

DEVIATION FROM ABOVE MOST ACCEPTED DEFINITION:

Colchicine and ricinine are acidic in nature but still regarded as alkaloids.

RICININE

Ephedrine and muscuraine are regarded as alkaloids although they do not contain nitrogen as a part of heterocyclic ring.

MUSCURAINE

Thiamine although has heterocyclic nitrogenous base, but not regarded as alkaloid

Caffeine fully satisfy the definition but included in alkaloids as it is not formed by amino acid.

CAFFIENE

Forms of Alkaloids:
Free bases Salts with Organic acids e.g. Oxalic, acetic acids
Salts with inorganic acids e.g. Hcl, H2SO4. Salts with special acids: e.g. Meconic acid in Opium, Quinic acid in Cinchona Glycosidal form e.g. Solanine in Solanum

OCCURANCE and DISTRIBUTION

a).Ranunculaceae :
b). Legumioceae :

Aconitine (aconite).
physostigmine (physostigma) strychnine and Brucine (Nux-

.
c).loganiaceae: vomica). d).Papavaraceae : (Opium). e).Solanaceae :

Morphine, Codiene,

Thebaine

hyoscine (Belladona).

f).berberidaceae
g).Rubiaceae: h). Apocyanaceae

Berberine (Berberis).
Quinine and Quinidine (Cinchona). : Reserpine (Rauwolfia) , Vincristine and Vinblastine (Vinca).

i). Liliaceae

: Veriterine (Veratrum).

j).Clavicipitaceae

Ergotamine and Ergometrine (Ergot).

OTHER SOURCES

. castoramine :--- from Canadian beaver (The Canadian beaver is the largest rodent in North America).

Pyocyanine :-- from Pseudomonas aeruginosa (a bacteria).

Muscopyridine :--From Musk of an Deer.

NOMENCLATURE of ALKALOIDS
The genus of the plant such as Atropine from Atropa belladonna

The plant species (specific name (, such as Cocaine from Erythroxylon coca The common name of the drug, such as Ergotamine from ergot

 The name of the discoverer, such as Pellerierine that was discovered Pelletier

The physiological action they produce, such as Emetine that acts as emetic . prominent physical character they have, such as Hygrine .

PREFIXES & SUFFIXES

Prefixes:

-''Nor''- designates N-emethylation e.g. norpseudoephidrine -''Apo''- designates dehydration e.g. Apo-morphine . -''Iso''-, pseudo-, neo-, and epi-'' indicate different types of isomers .

 Suffixes: ''dine'' designates isomerism as in the case of the Cinchona alkaloids, quinidine and cinchonidine. ''ine'' indicates a lower pharmacological activity e.g. ergotamine is less potent than ergotamine

GENERAL PROPERTIES OF ALKALOIDS

PHYSICAL PROPERTIES :
a).Most alkaloids are crystalline solid , but some are liquid e.g.
Volatile; --Nicotine , Coniine .Spartine.

Non-Volatile:- Pilocarpine , Hyoscine

b).Majority of alkaloids are colorless but some are colored, e.g

Colchicine and Berberine are Yellow.

Canadine is Orange.

BERBERINE

CANADINE(calcium channel blocker):tetrahydroberberine.

C). SOLUBILITY :-difference in solubility used as a base for their isolation and purification from nonalkaloidal bases.
The following can be mentioned :-

a).Both alkaloidal base and there salts are soluble in alcohol. b).Genarally bases are soluble in organic solvent and alkaloidal salts are soluble in water.

Alkaloid or its Salt Water Atropine Atropine sulphate Morphine Morphine sulphate 460 0.5 3400 15.5 Alocohol Ether 2 5 300 565 25 Insoluble 5000 Insoluble Chlorofor m 1 Insoluble 1525 Insoluble

EXCEPTION :
A).Bases soluble in water:--Caffeine, Codeine, Ephedrine. B).Bases in-soluble or sparingly soluble in certain organic solvent :Morphine in ether(1:5000), C).Salt insoluble in water :---Quinine sulphate quinine sulphate is only soluble in water to the extent of 1:1000 , although quinine hydrochloride is soluble 1 in less than l part of water

D).Salts soluble in organic solvents :---Lobelline and Apo atropine

Hcl are soluble in chloroform.

CHEMICAL PROPERTIES :
1).Salt formation :--Due to their basic character
alkaloid reacts with acid to form salt --strong bases form salt with very weak acid. --weak bases forms salt with strong acid -- very weak bases form unstable salts.e.g

caffeine , Narcotine , piperine.

2).amphoteric

Alkaloids :--can form salts with both

acid and alkali.

e. g. phenolic group :--Morphine

Carboxylic group:--Narciene (a narcotic alkaloid that occurs in opium).

3). Effect of heat:

Alkaloids are decomposed by heat, except Strychnine and caffeine (sublimable).

4). Effect of light and Oxygen :

Decomposed when allowed to stand at a temperature above 70o C .for long time. sensitivity varies in degree with different alkaloids. Decomposition occur rapidly and easily when an alkaloid is in solution than when it is in dry form. Most tertiary amine alkaloids are easily transformed to the N-oxides.

5).Reaction with acids: Salt formation. Dil. acids hydrolyze Ester Alkaloids e.g. Atropine Conc. acids may cause :

Dehydration:

Atropine Apo atropine Morphine Apomorphine Demethoxylation e.g. Codeine

6.Effect of alkalis.
Weak alkalis liberate most alkaloids from their salts e.g. NH3 Strong alkalis: such as aqueous NaOH and KOH form salts with phenolic alkaloids. Hot alkalis: results hydrolysis of ester alkaloids e.g. atropine, cocaine and physostigmine and cleavage of lactone ring, if present, to produce the corresponding acid, e.g. pilocarpine is transformed to pilocarpic acid.

7).BASICITY OF ALKALOIDS :--The basicity of alkaloid is due to presence of a lone pair of electron on nitrogen atom.

--the basicity increased if the adjacent group is electron releasing like alkali . -- the basicity decreases if the adjacent group is electron withdrawing like carbonyl and amide group.

R2-NH > R-NH2 > R3-N

Examples of electron withdrawing groups halogens (F, Cl) nitriles (CN) carbonyls (CO). nitro groups (NO2). Examples of electron releasing groups are

alkyl groups. alcohol groups. amino group.

According to basicity Alkaloids are classified into:

a). Weak bases e.g. Caffeine
b). Strong bases c). Amphoteric
e.g. Atropine

* Phenolic Alkaloids e.g. Morphine

*Alkaloids with Carboxylic groups e.g. Narceine

d). Neutral alkaloids e.g. Colchicine

 Primary amines (R-NH2 ) e.g. Norephedrine

Secondary amines (R2-NH) e.g. Ephedrine

Tertiary amines (R3-N)

e.g. Atropine

Quaternary ammonium salts (R4-N ) e.g. d-Tubocurarine

Note :--Unsaturation decreases the basicity e.g. piperidine is more basic than pyridine alkaloid.

BIOSYNTHESIS OF ALKALOIDS :
It is well established that alkaloids are derived from Amino acid.

the most common ones are: phenylalanine, tyrosine, lysine, ornithine, histidine, tryptophan and anthranilic acid.

EXTRACTION OF ALKALOIDS

Any method will be a good technique, if it will accelerate: 1. Wetting of the surface of the herb particles.

2. Permeability of cell walls.

3. Rate of dissolution of cell contents in the solvent. 4. Outward diffusion of the solution.

IDEAL PROPERTY OF SOLVENT

1. It should be non-toxic and selective. 2. It should not cause the extract to complex or dissociate. 3. It should be preservative in action. 4. It should promote rapid physiologic absorption of the extract. 5. It should be easily evaporated at low heat. NOTE:- Alcohol (Ethanol) will meet all above criteria.

SELECTION OF ALKALI
1. use of strong alkali not recommended in case of fatty drug e.g. seeds to avoid saponification, which results in strong emulsion during extraction. 2.Salts of strong base with mineral acid need the use of stronger alkali than those of weak base with organic acids.

3.Ammonia is a alkali of choice as it is sufficiently basic to liberate most of alkaloid , as well as ,volatile and completely removed after extraction.

Solvents
1.Organic water-immiscible solvent:-Chloroform, Benzene , ether, ethylene chloride.
Use:--they are use to extract most of alkaloid except quarternary ammonium bases .

2.Organic water-miscible solvent:--Ethyl and Methyl alcohol.

Use:-extract both alkaloid and their salts.

3.Aqeous acid:--Cheap but not used because it also extract impurities like sugar, mucilage, tannins, coloring matter

STAS-OTTO METHOD
The technique involve the distribution of alkaloidal bases between acid or aqueous solution and immiscible organic solvent.

Method I:
The powder is treated with alkalis to liberates the free bases that can then be extracted with water immiscible organic solvents.

A). stage1:--Powdered material is moistened with water and

mixed with alkali like sodium & potassium carbonate , ammonia, lime. Make a paste with water ,dry ,repowder.

Concept :--Lime(calcium hydroxide),combines with acid , tannins, and other phenolic substances and sets free alkaloids.

Method 1

Powdered drug Containing alkaloidal salts

Defatted if necessary

Free alkaloids Total extracts

Moisten & render alkaline with Na2CO3, lime, NH3 Exhaust with org. solvent like CHCl3, ether

Conc. & shake with acid like dil. H2SO4

Aq. Acid soln

(Alkaloidal salts)
Make alkaline extract with immisicible solvent

Residual organic fraction

(pigments, fats & weak bases or chloroform soluble alkaloids sulphates)

Residual aq. Fraction

organic soln (alkaloidal bases)

Remove solvent

crude alkaloidal mixture

B).Stage2:-- Extract the free alkaloids by hot continous

percolation with chloroform or any other organic solvents.

Concept :-The free alkaloids dissolve together with other

substances soluble in solvent.

C).Stage3:--Agitate the chloroform soln. with successive portion

of dil.sulphuric acid separating the aqueous layer before adding the next portion of acid.

Concept :-The alkaloids are converted into alkaloidal sulphates, which being soluble in water,pass into aqeous layer.

D).Stage4:--Make the mixed aqueous liquid alkaline with

ammonia, collect the precipitate that forms, wash with water and dry.

Concept :- Ammonia decomposes the alkaloidal sulphates forming ammonium sulphates ,soluble in water ,and the free alkaloid which being practically insoluble in water is precipitated.

Method I I:
The powder is extracted with water soluble organic solvents such as MeOH or EtOH which are good solvents for both salts and free bases. And the resultant extract is submitted to same process as that of method1.

ADVANTAGE :-- This method requires no alkali, gives good penetration of drug ,therefore only 4 extraction may be needed , whereas method1 requires 10-12 extraction, i.e. Economical.

Method III:
The powdered material is extracted with water or aqueous alcohol containing dilute acid.

Disadvatage:-- Cheap but not used because it also extract impurities like sugar, mucilage, tannins, colouring matter.

PURIFICATION OF ALKALOIDS :
1.DIRECT CRYSTALLISATION FROM SOLVENT.

2.STEAM DISTILLATION.
3. CHROMATOGRAPHY TECHNIQUES. 4. GRADIENT pH TECHNIQUES.

GRADIENT pH TECHNIQUES
Though alkaloids are basic in nature, there are variations in the extent in the basicity of various alkaloids of the same plant.

Depending on this character, the crude alkaloidal mixture is dissolved in 2% tartaric acid solution and extracted with benzene so that the first fraction contains natural and/or very weakly basic alkaloids.
pH of the aqueous solution is increased gradually by 0.5 increment upto pH 9, and extraction is carried out at each pH level with organic solvent, by this way alkaloids with different basicity are extracted. Strongly basic alkaloids are extracted at the end.

GENERAL CHEMICAL TESTS FOR ALKALOIDS PRECIPITATION REACTION :

1- Mayer's or Valser's reagent ( Potassium mercuric iodide) gives white or yellow color mostly amorphous precipitates with alkaloids,except the purine bases, ephedrine Colchicine and ricinine . Mercuric chloride 1.36 Potassium iodide 5.00 g Water to make 100 ml.

2. Wagner's reagent (Iodine- potassium iodide):- It

produces brown or reddish- brown precipitates with all alkaloids. Iodine 1.3 g Potassium iodide 2.0 g Water to make 100 ml

3.Dragendorff's or Krauts reagent ( potassium iodide+ bithmus nitrate):- It produces orange red precipitate which is usually
amorphous. Bismuth nitrate 8.0 g Nitric acid 20.5 g Potassium iodide 27.2 g Water to 100 ml

4. Hager's reagent (picric acid):- Gives

precipitate.

yellow crystalline

5. Tannic acid solution: (5%w/v) .:--gives buff colored ppt. which is soluble in dil.acid or ammonia.

6.Ammonium reineckate solution : 2% solution, produces precipitates with heterocyclic nitrogen alkaloids, with quaternary and some tertiary amines.

COLOUR REACTION
A). Van-Urks test: (Para-dimethyl-amino-benzaldehyde + sulphuric acid)-- (for Egot alkaloids).-gives Blue colour. B). Vitali-Morin test:-- test for solanceous alkaloids gives violet
colour when treated with conc. nitric acid and alcoholic KOH.

Mechanism :-- These color tests usually depend upon dehydration or oxidation of the alkaloid with a resultant characteristic color. Merits :-- a). very sensitive b). the intensity of the colour so formed is in linear proportion to the concentration of the alkaloid

METHOD FOR STRUCTURE ELUCIDATION U.V. Spectroscopy IR Spectroscopy Nuclear Magnetic resonance spectroscopy Mass spectroscopy Optical rotatory dispersion & circular dichroism. Conformational Analysis X-Ray diffraction

ROLE OF ALKALOID IN PLANTS

1. As reservoir of nitrogen.

2. As reservoir for protein synthesis

3. afford plant safety from herbivorous and insects. 4. might have possible role as growth regulatory factor. 5.acting as carrier within plants for transportation of such acids.

PHARMACOLOGICAL ACTIVITY
1. Analgesics and narcotics: 2. CNS stimulants : 3. Anticancer: 4. Mydriatics: 5. Anti-asthmatics : 6. Anti-tissue: 7. Expectorants: 8. Anti- hypertensive: 9. Smooth muscle relaxants: 10. Skeletal muscle relaxants: 11. Anthelmintics: 12. Antiparasitics: morphine and codeine. caffeine and strychnine. vincristine, vinblastine and taxol. atropine. ephedrine. codeine. lobeline. reserpine. atropine and papaverine d- tubocurarine. pelletierine and arecoline. quinine and emetine.

CLASSIFICATION
1. The pharmacological action (biological activity).

2. The chemical structure (heterocyclic or noheterocyclic type of ring structure). 3. The biochemical origin (biosynthetic pathway of production in the plant).
4. The taxonomical origin (plant families rich in alkaloids).

According to Robinson: Ornithine alkaloids: Lysine alkaloids: Phenylalanine alkaloids: Tryptophan alkaloids: Histidine alkaloids: Terpenoids alkaloids: Purine alkaloids:

Alline alkaloids:

Hegnauer's classification
1)."True alkaloids", which contain nitrogen in the heterocyclic ring and originate from amino acids. examples are atropine, nicotine and morphine, Quinine. All the heterocyclic alkaloids are true alkaloids. The true alkaloids should have following characters: a).It should be sufficiently toxic. b).should have marked physiological activity. c).should be basic in nature. d).Nitrogen should be present in a heterocyclic ring. e).Should be derived from amino acids. f).should occur in plant as salt of organic acids.

.PROTO-Alkaloids:- These are alkaloids which are derived from amino acid but do not have nitrogen in a heterocyclic ring. They are also called as Biological amine. Examples include:- mescaline, adrenaline and ephedrine.

.PSEUDO-Alkaloids:--They do not derived from amino acid but

having nitrogen in heterocyclic ring .

They do not show many of the typical characters of alkaloids , but give standard qualitative test for alkaloids.
e.g. steroidal alkaloids:-conessine
Purine bases :-- Caffeiene

CHEMICAL CLASSIFICATION :-- According to chemical structure, two broad division may be recognized: Non-heterocyclic alkaloids that are sometimes called ''proto alkaloids' or biological amines.

Heterocyclic alkaloids, that are sub-classified into different groups according to their ring structure.

HETEROCYCLIC ALKALOIDS

PYRROLE and PYRROLIDINE

Hygrine , stachydrine

PYRROLIZIDINE

sYmphitine , ehimidine.

PYRIDINE and PIPERIDINE

Nicotine , Coniine , Arecoline , Lobeline , Pelletierine

TROPANE

Cocaine , atropine , Hyoscyamine , Hyoscine

QUINOLINE

Quinine , quinidine , Cinchonine

ISO-QUINOLINE

Morphine , Codeine , Berberine , Emetine ,Tubocurarine , Papverine

APORPHINE (reduced Isoquinoline and naphthalene)

Boldine

NORLUPINANE

Lupanine , sparteine

INDOLE or BENZO-PYRROLE.

Ergotamine , ergometrine , Physostigmine , Reserpine, Strychnine , Brucine.

IMIDAZOLE

Pilocarpine.

PURINE (Pyrimidine+imidazole)

Caffeine , Theobromine

STEROIDAL (cyclo pentanoperhydrophenanthrene)

Conessine , solanidine

NON-HETEROCYCLIC :--

1.Ephedrine
2. Colchicine 3.Erythromycin 4.Mescaline

5. Taxol

Quantitative Determination of Alkaloids

1.Volumetric methods:
These are based on reaction of alkaloidal bases with acids (Acid-Base titration).They include:
a). Aqueous titration: This is carried by either: Direct titration of the alcoholic solution of the alkaloidal residue with standard acid, or Back titration by dissolving the residue in a known amount of standard acid and back titration of residual acid against standard alkali. b).Non-aqueous titration: This method is suitable for determination of weak bases e.g. Caffeine

2. Gravimetric methods:
These methods are recommended for determination of: 1- Very weak bases which can not be determined by volumetric methods e.g. caffeine and Colchicine. 2- Mixtures of alkaloids that are obtained from the same plant but differ greatly in their molecular weight e.g. Cinchona and Rauwolfia alkaloids. They can be performed by either:

1- Direct Weighing of the alkaloidal mixtures 2- Precipitation of the total alkaloids and determination of the weight of the precipitate obtained.

The major drawbacks of the gravimetric methods are:

1- They are insensitive to micro-amounts of alkaloids.

2- They could not be applied in case of thermolabile and volatile alkaloids.

3- Lipophilic impurities in the residue are calculated as alkaloids.

SOME IMPORTANT DRUGS

EPHEDRINE :---(SynonymMa-huang).
B.S It consists of dried young stem of Ephedra gerardiana and Ephedra nebrodensis. Family:-Gnetaceae(Ephedraceae). C.C:-- It contains the amino alkaloids : Ephedrine, nor-ephedrine, nmethyl ephedrine, pseudo-ephedrine.

Test :-- Ephedrine is dissolved in water and dil.hcl ,then treated separately with copper sulphate and sodium hydroxide. The solution gives Violet colour. If shaken with ether the organic layer shows purple colour and aqueous layer shows blue colour. Uses :-- a).bronchodilator in asthma. b).in the treatment of allergic condition like hay fever.

COLCHICUM :-B.S :--It consists of dried ripe seeds of Colchicum luteum and Colchicum autumnale. Family :--Liliaceae. C.C :-- Colchicine and Demi-colchicine.(both the alkaloids contain Tropolone ring structure).

Colchicine is freely soluble in alcohol and chloroform , soluble in 25 parts of water and in 220 parts of ether. Test - Colchicine + 70% H2SO4 Yellow colour.

Uses :-- Specific drug for treatment of Gout and also having Anti-Tumor activity.

A).ARECA :- It consists of dried ripe seeds of Areca catechu.

Family :-- Palmae. C.C :-- Arecoline, Guvacine, Guvacoline.

ARECOLINE
Uses :-Having Parasympathomimetic action --Sialogogue property and used in Paan-Supari. Areca is an Anthelmintic drug used in veterinary practice.

RAUWOLFIA :-- (Sarpagandha , serpentine root).

B.S.-- It consists of dried roots of plant Rauwolfia serpentina Family :-- Apocyanaceae. C.C :-- Reserpine .

Other alkaloids are :-- Ajamaline , Ajamalicine , resepinine , yohimbine , serpentine and serpentinine.

Test :--

Reserpine + vanillin in Acetic acid

RED colour.

Uses :-- Anti-Hypertensive.

OPIUM :-- It is the dried latex obtained by incision from the unripe capsule of Papaver
somniferum.

Family :-- papavarceae. (It should not contain less than 9.5% of morphine calculated as anhydrous morphine. Phenanthrene type :-Morphine , Codeine , Thebaine. C.C :-- Benzylisoquinoline type :-- Narcotine (noscapine), Narceine , Papaverine.

Codeine
.

NARCOTINE

Test :--1.Meconic acid test :-- opium is dissolved in water . filter , and to filterate ferric chloride is added by which deep reddish purple colour is obtained ,which persists even on addition of Hcl. 2. Morphine when sprinkled on nitric acid gives orange red colour. Codeine does not respond to this test. 3.Papaverine + Hcl + Potassium ferricyanide Lemon yellow colour

Uses :-- a).Morphine is a potent analgesic. b).Codeine is an anti-tussive. c). Papaverine has relaxant effect on smooth muscles of intestine and bronchial tract.

BELLADONA :-- ( Deadly night shade leaf). B.S :-- It consists of dried leaves and other aerial parts of Atropa belladonna.

Family :-- Solanaceae C.C :-Atropine , Hyoscyamine , Hyoscine , Homatropine.

ATROPINE

Test :--(VITALIMORIN TEST ):-The tropane alkaloid is treated with fuming nitric acid , followed by evaporation to dryness and addition of methanolic KOH solution to an acetone solution of nitrated residue.Violet colouration takes place due to tropane derivative. Uses :-- a). anti-cholinergic properties.( Pre- anaesthetic agent). b).Anti-dote in opium and chloral hydrate poisoning.

CINCHONA :-- It is the dried bark of cultivated trees of Cinchona calisaya Cinchona ledgeriana Cinchona officinalis Cinchona succirubra Family :-- Rubiaceae. C.C ;-Quinine , Quinidine , Cinchonine and cinchonidine. Also contains Quinic and Cinchotannic acid. Glycoside -- Quinovin Tannins and Bitter essential oil. Test ( THALLEOQUIN TEST) :--

Cinchona powder + Bromine water + dil. Ammonia Emarld green colour. Uses :-a). Anti-malarial. b). anti-Pyretic. c).stomachic d). Quinidine is used in Arrhythmia and tachycardia.

Conclusion
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.

REFRENCES :-

Trease, G. E. And Evans, W. C. Pharmacognosy, 12th Edition Pharmacognosy by Kokate C. K., A. P. Purohit and S.B. Gokhale , Nirali prakshan ,21st edition. R.M. Mehta Text Book Of Pharmacy. Natural Products (Alkaloids) Mohab Zaho El-didamoni B.SC.in Chemistry Dr.Hamady Abd El-Azeem Suez canal university Faculty of science Chemistry department 2009 Essential of pharmacognosy by Dr. S.H.Ansari , Birla publication ,3rd edition. http://en.wikipedia.org/wiki/Alkaloid Phytochemisry (alkaloids) by Dr. Mazen A. El-Sakka, Al-Azhar University, Faculty of pharmacy ,3rd edition . ALKALOIDS. ELZBIETA & HANS BRAND, ELZBIETA COSMETICS BV, THE NETHERLANDS Text book of Organic chemistry by Bahl & Bahl .

REFRENCES :
Trease, G. E. And Evans, W. C. Pharmacognosy, 12th Edition Pharmacognosy by Kokate C. K., A. P. Purohit and S.B. Gokhale , Nirali prakshan ,21st edition. R.M. Mehta Text Book Of Pharmacy. Natural Products (Alkaloids) Mohab Zaho El- didamoni B.SC.in Chemistry Dr.Hamady Abd El- Azeem Suez canal university Faculty of science Chemistry department 2009 Essential of Pharmacognosy by Dr. S.H.Ansari , Birla publication ,3rd edition. http://en.wikipedia.org/wiki/Alkaloid Photochemistry (alkaloids) by Dr. Mazen A. El- Sakka, Al- Azhar University, Faculty of pharmacy ,3rd edition . ALKALOIDS. ELZBIETA & HANS BRAND, ELZBIETA COSMETICS BV, THE NETHERLANDS Text book of Organic chemistry by Bahl & Bahl .