alkaloids

Alkaloids

Mr. Vishal Suresh Bagul S.Y.M.Pharmacy Department of PharmacogonyR.C.Patel Institute of Pharmaceutical Eduction & Research ,Shipur

Definition

• Alkaloids are basic nitrogen containing compounds. They are generally obtained from plants, animals and microorganisms and often demonstrate a marked physiological action

Mr.Vishal S Bagul Department of Pharmacognosy,RCPIPER,Shipur

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 Origin: Some alkaloids are derived from Bacteria, Fungi,

Insects, Frogs, Animals.

• Biosynthesis: Some alkaloids are not derived from amino acids e.g

purine, steroidal alkaloid .


ALKALOID DESCRIPTION• Contains nitrogen -usually derived from an amino acid.

• Bitter tasting, generally white solids (exception -nicotine is a brown liquid).

• They give a precipitate with heavy metal iodides. • Caffeine, a purine derivative, does not precipitate like most alkaloids.

• Alkaloids are basic -they form water soluble salts. Most alkaloids are well-defined crystalline substances which unite with acids to form salts. In plants, they may exist

• in the free state, • as salts or • as N-oxides. • Occur in a limited number of plants. Nucleic acid exists in all plants,

whereas, morphine exists in only one plant species .


TESTS FOR ALKALOIDS• Most alkaloids are precipitated from neutral

or slightly acidic solution by • Dragendorff's reagent (solution of potassium

bismuth iodide)orange coloured precipitate. • Mayer's reagent (potassio mercuric iodide

solution) Cream coloured precipitate. • Wagner’s reagent (iodine in potassium

iodide) red-brown precipitate• Hagers reagent (picric acid) yellow precipitate• Caffeine does precipitate


OCCURRENCE, DISTRIBUTION& LOCATION OF ALKALOIDS• Occur in bacteria(Pseudomonas aeruginosa) and rarely

in fungi (pscilocin from hallucinogenic mushrooms).• Some alkaloids occur in several genera from different

species (caffeine), but most occur in closely related species.

• Some occur in certain families (hyoscyamine), while others occur only in a specific species (morphine).

• Rarely do plants contain more than 1 type of alkaloid. • All alkaloids of one plant will have a common

biogenenetic origin


• Alkaloids occur in all plant parts, but are usually localized in one organ (e.g. the bark or seeds).

• Within the plant, [alkaloid] can vary widely from part to part –some parts may contain no alkaloids.

• Occasionally, different alkaloids also form in different parts of the plant.

• Alkaloid concentrations occur in wide ranges –e.g. Madagascar periwinkle contains 3g per (anti-cancer) alkaloids per tonne of leaves.


PHYSICAL-CHEMICAL PROPERTIES OF ALKALOIDS• MW: 100 –900• Most bases which do not contain O2 are liquid at

room temperature (nicotine), while those that do are solids. In rare cases they are coloured.

• Most solid bases rotate the plane of polarized light, have high melting points.

• Normally are not soluble in water (occasionally slightly soluble).

• Soluble in a polar or slightly polar organic solvents. Soluble in concentrated hydroalcoholic solutions


• The basicity of alkaloids depends on the availability of the lone pair of e-on the N2 atoms: e-donating groups enhance basicity, while e-withdrawing groups decrease it.

• Because some alkaloids have a carbonyl group on the amide, they can also be neutral (colchicine & piperine).

• Basic characteristic renders complex alkaloids unstable, so that in solution they are sensitive to heat, light & oxygen.

• Basic character of alkaloids also allows them to form salts with mineral acids (such as hydrochlorides, nitrates and sulphates) or inorganic acids (tartrates, sulfamates).

• Alkaloid salts are soluble in water and dilute alcohols.• Solid salts can be conserved well and are a common

commercial form of alkaloids.


NAMING OF ALKALOIDSNumerous methods can be used to name alkaloids1-Generic plant name –atropine from Atropa belladonna2-Specific name of the plant –cocaine from Erythroxylum coca.3-Common name of the herb –ergotamine from ergot (rye)4-Physiological action of the plant –emetine producing emesis5-Other –e.g. morphine derived from ancient Greek mythology –Morpheus –god of dreams


EXTRACTION OF ALKALOIDS• Extraction is based on the basicity of alkaloids and on the fact that they

normally occur in plants as salts (i.e.: on the solubility of bases and salts in water and organic solvents).

• Herbs often contain other materials which can interfere with extraction such as large amounts of fat, waxes, terpenes, pigments and other lipophilic substances (e.g by forming emulsions) –avoided by defatting the crushed herb (using petroleum ether and hexane.

• Extraction method normally depends on the raw material, the purpose of extraction & the scale on which is to be performed.

• For research purposes: chromatography allows for quick and reliable results.

• If larger amounts of alkaloids need to be extracted, one of the following methods can be used.


GENERAL METHOD• Powdered, defatted herb is mixed

with an alkaline aqueous solution.• Free bases are then extracted with

organic solvents.• Normally aqueous ammonia is used,

but a carbonate solution is used when alkaloids contain fragile elements such as a ester or lactone.

• In some cases, e.g. Cinchona bark, a mixture of calcium hydroxide & sodium hydroxide should be used as the alkaloids are bound to tannins.

• Organic solvent: chloroform, dichloromethane or ethyl acetate –depends on the toxicity, safety, cost & ease of recovery and recycling of the solvent). Mr.Vishal S Bagul Department of Pharmacognosy,RCPIPER,Shipur

Step II

• Organic solvent containing alkaloids (bases) is separated from residue & concentrated by distillation under pressure if needed.

• Solvent is stirred with an acidic aqueous solution: alkaloids go into the solution as salts. Impurities remain in the organic phase.


• Aqueous solution of alkaloid salts is washed with an apolar solvent (hexane)

• Alkalinized with a base using an organic solvent not miscible with water.

• Alkaloids precipitate and dissolve in the organic phase.

• Extraction of aqueous phase continues till all alkaloids have moved into the organic phase (tested when Mayer’s reaction on the aqueous phase becomes negative).

• This purification step may be carried out in a separation funnel or in centrifugal extractors Mr.Vishal S Bagul Department of Pharmacognosy,RCPIPER,Shipur

• Step III• Organic solvent containing alkaloid bases is

decanted, freed from water traces (drying over anhydrous salt e.g. sodium sulphate) and evaporated under reduced pressure.

• A dry residue remains: total basic alkaloids.


Extraction of liquid alkaloids

2 Methods possible

1-Plant powder is extracted directly with

acidified water

2-Plant powder is extracted with acidified

alcoholic or a hydroalcoholic solution. This

is then followed by distillation under

vacuum (eliminates that alcohol, leaving

behind and acidic aqueous solution of

alkaloid salts)


Classification of Alkaloids1. Biological origin

Sedatives : MorphineVasodilatation : Ephedrine, Ergonovine . Local anesthetic : CocaineHallucinating : Mescaline, Psilocybin.


2-Biosynthetic pathway Ornithine- Tropane, Pyrrolidine, PyrrolizidineTyrosine-Benzyl isoquinolineTryptophane- Indole alkaloids, QuinolinePyridine- PyridineLysine- Quinolizidine, Piperidine


3- Chemical classification

• True (Typical) alkaloids that are derived from amino acids and have nitrogen in a heterocyclic ring. e.g Atropine

• Proto alkaloids 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.


A. Proto alkaloids

• These are also called Non heterocyclic or Atypical alkaloids or Biological amines.

• These are less commonly found in nature. • These molecules have a nitrogen atom which

is not a part of any ring system. • Examples of these include ephedrine,

colchicine, erythromycin and taxol etc. • Table below shows the chemical structure and

biological significance of these compounds:


Name Structure Biological Significance

Ephedrine

Adrenergic agent-used for asthma and hay fever

Colchicine

Relieves gout

Erythromycin

Antibiotic


Taxol (Paclitaxel)

Used in the treatment of ovarian cancer, breast cancer and non-small cell lung cancer


B. Heterocyclic Alkaloids or Typical Alkaloids:• Structurally these have the nitrogen as a

part of a cyclic ring system. • These are more commonly found in nature. • Heterocyclic alkaloids are further

subdivided into 14 groups based on the ring structure containing the nitrogen


No. Heterocycle Example

1.

Pyrrole and Pyrrolidine

Hygrine, Stachydrine

2.

Pyrrolizidine

Senecionine, Symphitine, Echimidine, Seneciphylline


3.

Pyridine and Piperidine

Lobeline, Nicotine, Piperine, Conine, Trigonelline

4.

Tropane (piperidine/N-methyl-pyrrolidine)

Cocaine, Atropine, Hyoscyamine, Hyoscine

5.

Quinoline

Quinine, Quinidine, Cinchonine, Cinchonidine


6.

Isoquinoline

Morphine, Emetine, Papaverine, Narcotine, Tubocurarine, Codeine

7.

Aporphine (reduced isoquinoline/naphthalene)

Boldine

8.

Quinolizidine

Lupanine, Cytisine, Laburnine, Sparteine


9.

Indole or Benzopyrole

Ergometrine, Vinblastine, Vincristine, Strychnine, Brucine, Ergotamine, Yohimbine, Reserpine, Serpentine, Physostigmine

10.

Indolizidine

Castanospermine, Swainsonine

11.

Imidazole or glyoxaline

Pilocarpine, Pilosine


12.

Purine (pyrimidine/imidazole)

Caffeine, Theobromine

13. Steroidal (some combined as glycosides)*

Conessine, Solanidine

14. Terpenoid*

Aconitine, lycaconitine, Aconine

*Note- Steroidal and terpenoid classes are also treated as separate classes or along with glycosides.


Biosynthetic classification1. Ornithine derived alkaloidse.g. Pyrrolidine alkaloid-nicotine Tropane alkaloid – Atropine, hyosyamine, coacaine2. Lysine derived alkaloids e.g. Piperidine and pyridine alkaloid – conine, lobaline, arecoline

Quinazolidine alkaloid- lupinine3. Tyrosine derived alkaloidse.g. Isoquinoline alkaloid – morphine, codeine, emetine, cephaline, berberine, d- tubocurine

Amino alkaloid- colchicine4. Tryptophan derived alkaloidse.g. Indole alkaloid- ergot alkaloid, vincristine, vinblastine, reserpine, strychnine, physostigmine, strychinine, brucine Quinoline alkaloid – cinchonine, quinine, quinidine, camptothecin5. Histidine derived alkaloidse.g. Imidazole alkaloid – Pilocrpine6. Phenylalanine derived alkaloidse.g. Amino alkaloid- Ephedrine


Pharmacological classification1. Narcotic analgesic e.g.Morphine

2. Antimalerial e.g. Quinine

3. Reflux excitability e.g.Strychnine

4. Respiratory stimulant e.g.Lobeline

5. Neuralgia e.g. Aconitine

6. Oxytocic e.g. Erogotometrine

7. Bronchodilator e.g. Ephedrine, vasicine

8. Anticholinergic e.g. Atropine

9. CNS stimulant e.g. Caffeine

10. Antitussive e.g. Codeine

11. Antiarrythmic e.g.Quinidine

12. Antihypertensive e.g. Reserpine

13. Anticancer e.g. Vincristine

14. Antiglucoma e.g. Pilocarpine Mr.Vishal S Bagul Department of Pharmacognosy,RCPIPER,Shipur

Biosynthesis of indole alkaloids


Biosynthesis of Isoquinoline alkaloids


Biosynthesis of Tropane alkaloids


Biosynthesis of Quinoline alkaloids


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alkaloids

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