Alkaloids.pptx

Description about crude drugs containing alkaloids.

1. ALKALOIDS By Dr. Rakesh Barik

2. Definitio n Alkaloids, which means alkali-like substances, are complex, heterocyclic, basic nitrogenous compounds of plant origin . Containing nitrogen inside or outside the heterocyclic ring, which may or may not be derived from amino acids. Generally possessing a marked physiological action on man or animals , at lower concentration. The term “ Alkaloid” was coined by the German chemist, Meissner.

3. Function s of alkaloids in plants 1. They may act as protective against insects and herbivores due to their bitterness and toxicity. 2. They are, in certain cases, the final products of detoxification in metabolic reactions, therefore considered as waste products of metabolism . 3. They may provide nitrogen to the plant organs in case of nitrogen deficiency ( source of nitrogen ). 4. They, sometimes, act as growth regulators in certain metabolic systems. 5. They may be utilized as a source of energy in case of deficiency in carbon dioxide assimilation, especially those alkaloids containing a sugar moiety .

4. Some alkaloids are extremely poisonous e.g.: Ergot alkaloids caused epidemic poisoning in the Middle Ages in Europe as a result of feeding on rye bread contaminated with the fungus. The extracts of plants containing such alkaloids have long been used as arrow poisons in hunting and warfare e.g. curare extract that contains tubocurarine alkaloid. Certain were employed in this respect, as a draught for execution e.g. Socrate’s execution, in ancient Greece, with hemlock which contains coniine .

5. At the time of the Roman Empire, Belladonna (the source of atropine) has been mixed with food with the purpose of murdering. Cleopatra, the queen of Egypt used Egyptian henbane ( Hyoscyamus muticus ) that contains hyoscyamine , for suicidal purpose. Certain alkaloids are widely used for their psychotropic effects e.g. caffeine acts as CNS stimulant and nicotine is responsible of the psychological and physical dependence of tobacco . Usage History

6. No m enclatu r e: Alkaloids terminate with the suffix-ine, their names may be derived from the: Atropine from Atropa. Cocaine from Coca. Common name, e.g., Ergotamine from Ergot. Physiological activity, e.g. Emetine (emetic). Genus name e.g., Species name, e.g.,    Discoverer, e.g., Pelletierine from Pelletier.

7. Prefixes and suffixes: Prefixes: "Nor-" designates N-demethylation e.g. Norpseudoephedrine and Nornicotine. "Apo-" designates dehydration e.g. Apomorphine. "Iso-, pseudo-, neo-, and epi-“ indicate different types of isomers. Nornicotine Nicotine Morphine Apomorphine

8. Suffixes: N H H H HO H N R N H H H H H O R (-)-Quinine (-)-Cinchonidine R = OCH 3 R = H N (+)-Quinidine (+)-Cinchonine R = OCH 3 R = H "-dine" designates isomerism as in the case of the Cinchona alkaloids, quinidine and cinchonidine are the optical isomers of quinine and cinchonine, respectively . Cinchona Alkaloids

9. Classification Different systems of classification based on: The pharmacological action (biological activity) The chemical structure (type of nitrogen, heterocyclic or non-heterocyclic and type of ring structure) The biochemical origin (biosynthetic pathway of production in the plant) The taxonomical origin (plant families rich in alkaloids)

10. According to Hegnauer’s classification , which is based on both the type of nitrogen and the biochemical origin , three main types of alkaloids are distinguished: True alkaloids: these are derived from amino acids and have nitrogen in a heterocyclic ring. Show positive results for the general chemical tests. Protoalkaloids: these are derived from amino acids and have nitrogen outside the heterocyclic ring. Show positive results for the general chemical tests. Pseudo alkaloids: these are not derived from amino acids but have nitrogen in a heterocyclic ring. Show negative results for the general chemical tests.

11. CLASSIFICATION OF ALKALOIDS 1) Pharmacological action (Biological activity) Analgesics e.g. Morphine and Codeine CNS stimulants e.g. Caffeine and Strychnine Anti-cancers e.g. Vincristine, Vinblastine and Taxol Mydriatics e.g. Atropine Myotics e.g. Pilocarpine Anti-asthmatics e.g. Ephedrine Anti-tussives e.g. Codeine Expectorants e.g. Lobelline Anti-hypertensives e.g. Reserpine Smooth muscle relaxants e.g. Atropine and Papaverine Skeletal muscle relaxants e.g. Tubocurarine Anthelmintics e.g. Pelletierine Antiparasitics e.g. Quinine and Emetine

12. Chemical structure A-types of nitrogen, Heterocyclic or non- heterocyclic B- according to type of ring structure. Non-Heterocyclic or atypical alkaloids Sometimes called Protoalkaloids or Biological amines e.g. Ephedrine, Colchicine, and Taxol. All have exocyclic N-atoms. b) Heterocyclic or typical alkaloids which sub- divided into several groups according to their ring structure.

13. Classification of alkaloids Chemical classification A) True alkaloids Sr. no. T y p e Structure Examples 1. Pyrrole and pyrrolidine N H N H e.g. Hygrine, coca species 2. Pyiridine and piperidine N N H e.g. Arecoline, anabasine, lobeline, conine, trigonelline 3. Pyrrolizdine N e.g. Echimidine, senecionine, seneciphylline 4. Tropane N e.g. Atropine, hyoscine, hyoscyamine, cocaine, pseudopelletirine 5. Quinoline N e.g. Quinine, quinidine, cinchonine, cupreine, camptothecine 6. Isoquinoline N e.g.Morphine, codeine, emetine, cephaline, narcotine, narceine, d- tubocurarine

14. 7 I n d o l e N H e.g. Erotamine, ergotametriene, reserpine, vincristine, vinblastine, strychnine, brucine 8 Imidazole N N H e.g. Pilocrpine, isopilocarpine, pilosine 9 N o r l u p i n a n e N e.g. Cystisine, laburinine 10 A porphine (reduced i s o q u i n o li ne napthalene) N e.g. Boldine

15. B) PROTOALKALOID 1. Alkyalamine Ephedrine, Pseudoephedrine H O NH C) Pseudoalkaloid 1. Pu r i ne N N N H N e.g. Caffeine, thophylline, theobromine 2. Steroidal e.g. Solanidine, conessine, protoveratrine 3. Diterpene C 20 H 32 e.g. Aconitine, aconine, hypoaconine

16. 3- Alkaloids are classified according to the amino acid that provides both the nitrogen atom and the fundamental portion of the alkaloid skeleton. Amino acid Alkaloid skeleton Ornithine Pyrrolidine and tropane alkaloids Lysine piperidine, quinolizidine, and indolizidine alkaloids Nicotinic acid pyridine alkaloids Tyrosine phenylethylamines and simple tetrahydroisoquinoline alkaloids, Tryptophan simple indole, simple β-carboline, terpenoid indole, quinoline, pyrroloindole, and ergot alkaloids Anthr a ni l ic acid acts as a precursor to quinazoline, quinoline and acridine alkaloids Histidine imidazole derivatives

17. Biosynthetic Classification In this particular instance the significance solely lies to the precursor from which the alkaloids in question are produced in the plant biosynthetically. Indole alkaloids derived from tryptophan. Piperidine alkaloids derived from lysine. Pyrrolidine alkaloids derived from ornithine. Phenylethylamine alkaloids derived from tyrosine. Imidazole alkaloids derived from histidine.

18. Occurrence, Distribution & Location of Alkaloids  Occur in bacteria( Pseudomonas aeruginosa ) and rarely in fungi (pscilocin from hallucinogenic mushrooms).  Some occur in certain families (hyoscyamine), while others occur only in a specific species (morphine).  All alkaloids of one plant will have a common biogenetic 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 ton of leaves.

19.  All Parts e.g . Datura , Vinca .  Barks e.g. Cinchona  Seeds e.g. Nux vomica  Roots e.g. Aconite  Fruits e.g. Black pepper  Leaves e.g. Tobacco  Latex e.g. Opium Various Sources

20. Physical properties Occurrence : Most alkaloids are crystalline solids. Some are liquids , eg , Coniine, Nicotine Color: The majority of alkaloids are colourless but some are colored. e.g.: Colchicine and Berberine are yellow . Sanguinarine is red . Betanidine is orange. Taste: Bitter

21. S o lu b ili t y: Both alkaloidal bases and their salts are soluble in alcohol. Generally, the bases are soluble in organic solvents and insoluble in water Exceptions: Bases soluble in water: caffeine, ephedrine, codeine, colchicine, pilocarpine and quaternary ammonium bases. Bases insoluble or sparingly soluble in certain organic solvents: Morphine and psychotrine in ether, Theobromine and theophylline in benzene.

22. Salts are usually soluble in water and, insoluble or sparingly soluble in organic solvents. Exceptions: Salts insoluble In water: e.g. quinine monosulphate Salts soluble in organic solvents: e. g . Lobeline hydrochlorides soluble in chloroform.

23. Optical activity: Many alkaloids are optically active due to the presence of one or more asymmetric carbon atom (chiral) in their molecule. Optically active isomers show different physiological activities. Usually, the l (-) isomer is more active than the d (+) isomer . e.g .: l-ephedrine is 3 times more active than d-ephedrine l-ergotamine is 3 times more active than d-ergotamine. Exceptions: d-Tubocurarine is more active than the corresponding l- form. Both quinine (l-form) and its d- isomer quinidine are active. The racemic dl-atropine is physiologically active .

24. Chemical Properties Most of the alkaloids are basic in nature, due to the availability of lone pair of electrons on nitrogen. The basic character of the alkaloid compound is enhanced if the adjacent functional groups are electron releasing . The alkaloid turns to be neutral or acidic when the adjacent functional groups are electron withdrawing like amide group which reduces the availability of the lone pair of electron. Their salt formation with an inorganic acid prevents many a time their decomposition. In the natural form, the alkaloids exist either in Free State, as amine or as salt with acid or alkaloid N-oxides. The alkaloid may contain one or more nitrogen and exist in the form of Primary amines R-NH 2 e.g . Norephedrine Secondary amines R 2 -NH eg . Ephedrine Tertiary amines R 3 -N eg . Atropine Quaternary ammonium salts R 4 -N eg . D- ubocurarine

25. Tests for detection and identification Name of reagent Composition Observation Alkaloidal p r ec i pit a nts : 1.Mayer's test Wagner's test Hager's test Dragendorff's test Marmé's test Potassium-mercuric iodide Iodine in potassium iodide Saturated solution of picric acid Potassium bismuth iodide Potassium cadmium iodide Color of precipitate: Creamy white (positive with most alkaloids, except caffeine and dilute ephedrine). Reddish brown Yellow Orange-reddish brown Yellow precipitate

26. Specific Chemical Tests Alkaloids Name of Test Experiment Observation Tropane alkaloids Quinoline alkaloids Vitali Morin Test Thaleoquin Test The drug is treated with fuming nitric acid followed by evaporation to dryness. To the residue, acetone is added. Methanolic potassium hydroxide solution is then added. The drug powder is added with bromine water and dilute ammonia solution. Violet colour change is formed. Emerald green colour change is observed.

27. Alkaloids Name of Test Experiment Observation Opium alkaloids (Salts of Meconic acid) Purine alkaloids (Pseudo alkaloids) Meconic acid Test Murexide Test Opium is dissolved in water and filtered. To the filtrate, ferric chloride solution is added. The sample is taken in a petridish . Potassium chlorate and HCl are added and heated to dryness. The residue is exposed to dilute ammonia vapours . Dark reddish purple color is formed which persists on addition of HCl . Purple colour is observed which is lost upon addition of alkali solution.