Alkaloids

Definition: Definition: the term ³alkaloid´ (alkali-like) is (alkalicommonly used to designate basic heterocyclic nitrogenous compounds of plant origin that are physiologically active. active.

Deviation from Definition:
Basicity: Some alkaloids are not basic e.g. Colchicine, Piperine, Quaternary alkaloids.  Nitrogen: The nitrogen in some alkaloids is not in a heterocyclic ring e.g. Ephedrine, Colchicine, Mescaline.  Plant Origine: Some alkaloids are derived from Bacteria, Fungi, Insects, Frogs, Animals. 

Classification:
True (Typical) alkaloids that are derived from amino acids and have nitrogen in a heterocyclic ring. e.g Atropine  Protoalkaloids that are derived from amino acids and do not have nitrogen in a heterocyclic ring. e.g Ephedrine  Pseudo alkaloids that are not derived from amino acids but have nitrogen in a heterocyclic ring. e.g Caffeine  False alkaloids are non alkaloids give false positive reaction with alkaloidal reagents. 

New Definition: Alkaloids are cyclic Definition:
organic compounds containing nitrogen in a negative state of oxidation with limited distribution among living organisms. organisms.

Rubiaceae.  Dicots are more rich in alkaloids than Monocots. Solanaceae and Papaveracea. Labiatae  .  Families rich in Alkaloids: Apocynaceae.  Families free from Alkaloids: Rosaceae.Distribution and occurrence: Rare in lower plants.

g. Cinchona  Seeds e. Datura.g. Black pepper  Leaves e.Distribution in Plant:  All Parts e. Tobacco  Latex e.g.g.g. Nux vomica  Roots e.g. Aconite  Fruits e.  Barks e.g. Opium .

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

Source of nitrogen in case of nitrogen deficiency. products).Function in Plants      They may act as protective against insects and herbivores due to their bitterness and toxicity. They. in certain cases. toxicity. deficiency. assimilation. the final products of detoxification (waste products). systems. They may be utilized as a source of energy in case of deficiency in carbon dioxide assimilation. sometimes. act as growth regulators in certain metabolic systems. . They are.

 The plant species. such as Emetine that action. . such as Ergotamine from ergot. Erythroxylon coca. belladona. These names "ine". coca.  A prominent physical character.Nomenclature: Trivial names should end by "ine".  The common name of the drug. such as Hygrine character. acts as emetic. such as Atropine from Atropa belladona. may refer to:  The genus of the plant.  The physiological action. that was discovered by Pelletier. Morphine acts as narcotic. such as Cocaine from species.  The name of the discoverer. such as Pelletierine discoverer. that is hygroscopic.

a lower pharmacological activity e. in case of ergot alkaloids. and epi-" indicate different types of epiisomers. e. cinchonidine. Suffixes: Suffixes:  "-dine" designates isomerism as quinidine and cinchonidine. apomorphine.  "-ine" indicates. pseudo-. . ergotaminine is less potent than ergotamine.g. neo-. apomorphine.pseudo. ergotamine.g.  "Apo"Apo-" designates dehydration e. nornicotine.Prefixes and suffixes: Prefixes:  "Nor"Nor-" designates N-demethylation or N-demethoxylation.  "Iso. isomers. norpseudoephedrine and nornicotine.neo"Iso-.g.

:  Colchicine and berberine are yellow.g.g. copper- .  The salts of sanguinarine are copper-red.  Canadine is orange.Color: IIThe majority of alkaloids are colorless but some are colored e.g.Condition:    Most alkaloids are crystalline solids. Few alkaloids are amorphous solids e. emetine. Some are liquids that are either: Volatile e. II.Physical Properties: I. pilocarpine and hyoscine.g. or NonNon-volatile e. solids. nicotine and coniine.

codeine. ephedrine. Generally. chloroform.Solubility: IIIBoth alkaloidal bases and their salts are soluble in alcohol. alcohol. insoluble or sparingly soluble in organic solvents. bases. the bases are soluble in organic solvents and insoluble in water Exceptions: Exceptions:  Bases soluble in water: caffeine. water: monosulphate. solvents. Salts soluble in organic solvents: lobeline solvents: hydrochlorides are soluble in chloroform. pilocarpine and quaternary ammonium bases. benzene. and apoatropine   .Physical Properties: III.    Salts are usually soluble in water and. theobromine and theophylline in benzene. water: colchicine.  Bases insoluble or sparingly soluble in certain organic solvents: solvents: morphine in ether. Exceptions: Exceptions: Salts insoluble in water: quinine monosulphate.

Isomerization: IV      Optically active isomers may show different physiological activities. Quinine (l-form) is antimalarial and its d.5 times more active than d-ephedrine. 3d. l-ergotamine is 3-4 times more active than d-ergotamine.Tubocurarine is more active than the corresponding lform.isomer (l quinidine is antiarrythmic. l-ephedrine is 3. The racemic (optically inactive) dl-atropine is (optically dlphysiologically active. .IV.

.g.g.g. e. e.g Norephedrine Ephedrine Atropine d-Tubocurarine II.Basicity: II R2-NH > R-NH2 > R3-N  Saturated hexacyclic amines is more basic than aromatic amines.Chemical Properties: I.Nitrogen:     Primary amines RR-NH2 Secondary amines R2-NH Tertiary amines R3-N Quaternary ammonium salts R4-N e. e.

g.g. Morphine *Alkaloids with Carboxylic groups e.g. Atropine Amphoteric * Phenolic Alkaloids e.g.According to basicity Alkaloids are classified into:     Weak bases e. Colchicine .g. Narceine Neutral alkaloids e. Caffeine Strong bases e.

III. Nicotine.g.g. Atropine. Coniine. alkaloids are free from Oxygen and are mostly liquids e.Oxygen: III Most alkaloids contain Oxygen and are solid in nature e.  Some .

2.Stability: IV Effect of heat: heat: Alkaloids are decomposed by heat. with acids:  Reaction 1.IV. Atropine .Salt formation. except Strychnine and caffeine (sublimable).g.Dil acids hydrolyze Ester Alkaloids e. sublimable).

g.3. Codeine .Conc. acids may cause:  Dehydration: Atropine Apoatropine Morphine Apomorphine  Demethoxylation: e.

narceine. 3. NH3. .g.They also can form salts with alkaloids containing a carboxylic group e.Strong alkalis: such as aqueous NaOH and KOH form salts with phenolic alkaloids.g.Dil alkalis liberate most alkaloids from their salts e. Effect of Alkalies: 1. 5. 6.Strong alkalis cause hydrolysis of Ester alkaloids (e.Strong alkalis cause opening of lactone ring. cocaine and physostigmine) and Amide alkaloids ( colchicines). 2. 4. atropine.g.They may cause isomerization (racemization) of alkaloid as the conversion of hyoscyamine to atropine.

 Effect of light and Oxygen: Some alkaloids are unstable when exposed to light and Oxygen: Oxygen Eserine Alkaline solutions Rubreserine Reserpine Ergot Alkaloids Decomposition Lumi Alkaloids (Inactive) .

Test for complete of extraction Disadvantages: Some non alkaloids interfere such as Proteins.Qualitative test for Alkaloids:  Precipitation Reagents: They are used to: 1.Indicate the absence or presence of Alkaloids 2. coumarins . lactones.

Reagents that form double salts: 2.Silicotungestic Acid .Dragendorff¶s Reagents: Potassium Iodobismethate. Classification of Alkaloidal precipitating agents: a.Phosphomolybdic acid b. 1.Gold Chloride. c.Reagents Containing Halogens: a. b.Tannic Acid. 3-Organic Acids: a.Hager¶s Reagent: Picric Acid b.Phosphotungestic acid c.Wagner¶s Reagent: Iodine/ Potassium Iodide.Oxygenated High Molecular Weight Acids: a. 4.Mayer¶s Reagent: Potassium Mercuric Iodide.

HNO3 .Mandalin¶s Reagent: Sulphovanidic acid 4.Mecke's Reagent: Selenious acid / conc. H2SO4 6.Conc. HNO3/Conc. Colour Reagents: 1.Erdmann¶s Reagent: Conc. H2SO4 3.Rosenthaler's Reagent: Potassium arsenate / conc. H2SO4 8.Marqui¶s Reagent: Formaldehyde/ Conc. H2SO4 5.Froehd¶s Reagent: Phosphomolybdic acid 2.Shaer's Reagent: Hydrogen peroxide / conc. H2SO4 7.

Method II: The powdered material is extracted with water or aqueous alcohol containing dilute acid.Extraction. solvents. Method III: III: The powder is extracted with water soluble organic solvents such as MeOH or EtOH which are good solvents for both salts and free bases. impurities. . Alkaloids are extracted as acid. bases. Purification and Isolation of Alkaloids from Powdered plants  Extraction and purification Method I: The powder is treated with alkalis to liberates the free bases that can then be extracted with water immiscible organic solvents. their salts together with accompanying soluble impurities.

as salts) Alkaline aqueous layer .Plant material and solvent Organic solvent dissove Alkaloids Extract Organic solvent dissove Impurities Concentration Acidification Alkalinization Acidified Extract (Alk.

Lactone Alkaloids e. alkalis must be avoided in some cases: cases: 1.g. choice of strong bases. Pilocarpine 5.g.g. Solanaceous Alkaloids e. Colchicine 3. Morphine 4. Alkalis must be strong bases. However. enough to liberate free bases.Fatty Drugs due to saponification and emulsion formation.Amide Alkaloids e.g. .Ester Alkaloids 2.Phenolic Alkaloids e. Liberation of the free bases: Alkalis are used to liberate free bases.

Volatile so easy to get rid of it. MgO. Ca(OH)2.  Other Alkalis: Na2CO3. . NH4OH: Most widely used due to many advantages: 1. 2. 3.Strong enough to liberate most of alkaloids from their salts. NaHCO3.Milder than fixed alkalis so more safe.

 Ether: Gives cleaner Extract but have some disadvantages: 1. Extraction  CHCl3: of the free bases: Strong solvent can extract most of the alkaloids. Carcinogenic.High volatility 2. Extracts contain more impurities.High water miscibility .Peroxide formation 3.

. material + water + Fixed alkali Heat  Plant steam contain alkaloids received in acidic sloution.Volatile Alkaloids  The best way for their extraction is steam distillation.

 Repeated . agent.Purification of the Crude Alkaloidal Fractions: AcidAcid-Base procedures: Render extract Acidic. salts.  Precipitation with alkaloidal precipitating agent. organic solvent (dissolve non alkaloidal impurities). Alkaloids).  Convert to crystalline salts. Alkalinize and extract again with organic solvents (Dissolve Alkaloids). extract with Acidic.

Separation of Alkaloidal Mixtures:  Fractional Crystallization: oephe ri e alates Ephe ri e & se rystallizatio from water Ephe ri e alate rystals se oephe ri e Sol tio alate .

Atropine Hyoscyamineine Oxalates Crystallization from Acetone/Ether Atropine Oxalate Crystals Hyoscyamine Oxalate olution .

 Preparation of Derivatives: O Separation of Primary. filter Filtrate 1ry alk derivative Precipitate 2ry alk derivative . Mixture + p-toluenesulphonyl chloride Add l a d filter Cl S O Filtrate tertiary alkaloids as salt (no reaction with reagent 1ry alk derivative O R-HN S O acidic hydrogen OH R-N S O Precipitate 2ry alk derivative O keto form R-N S R O insoluble in alkalis enol form soluble in alkalis NaOH. Secondary and Tertiary Alkaloids.

2) Aqueous layer Atropi e & Hyoscyami e HCl (pKa = 9.Alkali ize by Na 2.5 Ether Hyosci e free base (pKa = 6.Extract with Ether 3 pH 7.3) . Fractional Liberation: Atropi e & yoscyami e & yosci e l salts the form of 1.

. Fractional Distillation: e. Separation of Nicotine and Anabasine  Chromatographic Separation.g.

GC. GC-MS GC UV. NMR. MS. . IR.Identification of Alkaloids:  Melting point  Colour test  Optical Rotation  Microcrystal test  HPLC.

Quantitative Determination of Alkaloids:     Volumetric methods: These are based on reaction of alkaloidal bases with acids (Acid-Base titration).Direct titration of the alcoholic solution of the alkaloidal residue with standard acid. .Back titration by dissolving the residue in a known amount of standard acid and back titration of residual acid against standard alkali. Caffeine. (AcidThey include: Aqueous titration: This is carried by either: 1.g. or 2. NonNon-aqueous titration: This method is suitable for determination of weak bases e.

2. The major drawbacks of the gravimetric methods are: are: 1. . 3.Direct Weighing of the alkaloidal mixtures 2.g. alkaloids.They could not be applied in case of thermolabile and volatile alkaloids.Precipitation of the total alkaloids and determination of the weight of the precipitate obtained.Mixtures of alkaloids that are obtained from the same plant but differ greatly in their molecular weight e. obtained. Cinchona and Rawolfia alkaloids. Gravimetric methods: These methods are recommended for determination of: of: 1.g. 2.Lipophilic impurities in the residue are calculated as alkaloids. alkaloids.Very weak bases which can not be determined by volumetric methods e. They can be performed by either: either: 1. caffeine and colchicine. alkaloids. alkaloids.They are insensitive to microamounts of alkaloids. colchicine.

Morphine + NaNO2/HCl Ergot + p-dimethylaminobenzaldehyde p-  Spectrophotometric  Polarimetric  Fluorimetric Methods. Methods  Chromatographic .g. Method. Method. Colourimetric Method: e.

According to the plant source of alkaloids. Primary. Secondary.  Botanical Source.Classification of Alkaloids  Biogenetic.  Type of Amines. Based on the biogenetic pathway that form the alkaloids. Tertiary alkaloids.  Basic Chemical Skeleton .

g. O . Phenylalkylamines: e. Ephedrine  Pyridine and piperidine e.g. lobeline. nicotine  Tropane e.g. Atropine.

 Quinoline e. papaverine N  Phenantheren e.g.quinine and quinidine  Isoquinoline e.g. Morphine .g.

caffeine 1 N 2 6 5 7 N H 8 N 4 3 Puri N 9 .ergometrine  Imidazole e.g.g.g. pilocarpine  Purine e. Indole e.

g. Steroidal e. Solanum and Veratrum alkaloids  Terpenoid e. Taxol .g.

Sign up to vote on this title
UsefulNot useful