Alkaloids

Alkaloids

1. ALKALOIDS BY NIVETHA.B M.PHARM

2. HISTORY OF ALKALOIDS: The term ‘ alkaloid ’ was coined by MEISSNER, a German pharmacist, in 1819. The French chemist, Derosne in 1803, isolated narcotine . In the same year , morphine from opium was isolated by Serturner . Pelletier and Caventon isolated emetine in 1817 and colchicine in 1819.

3. From the beginning of 19 th century till to date, it has to proved to be a perpetual work to discover new alkaloids from plants and animals. As per a Russian review in 1973, the numbe of known alkaloids had reached upto 4959, amongst which, the structures of 3293 alkaloids were elucidated.

4. At present, the number of alkaloids discovered has exceeded 6000.

5. What is alkaloid ? The term “alkaloid” (alkali-like) is commonly used to designate basic heterocyclic nitrogenous compounds of plant origin that are physiologically active . They resemble some of the characters of naturally occuring complex amines.

6. It posses specific physiological actions on human or animal body ,when used in small quantities. STRUCUTE OF ALKALOID

7. The term alkaloid also covers proto alkaloid , pseudoalkaloids and True alkaloids. TRUE ALKALOIDS: The true alkaloids are toxic in nature and contain heterocyclic nitrogen which is derived from amino acids and always basic in nature. True alkaloids are normally present in plants as salts of organic acids.

8. PROTOALKAOIDS: The ‘ protoalkaloids ’ or ‘amino alkaloids’ are simple amines in which the nitrogen is not in a heterocyclic ring. They are basic in nature and prepared in plants from amino acids PSEUDOALKALOIDS: It includes mainly steroidal and terpenoid alkaloids and purines.They are not derived from amino acids.

9. OCCURENCE OF ALKALOIDS: Alkaloids are occurs mostly in angiosperms and rarely in gymnosperms. But their presence is also detected in micro organisms, marine organisms, insects, animals and some of the lower plants. In the lower plants, although the alkaloids are found in less number, some important sources

10. are ergot fungus giving peptide alkaloids , ergometrine , ergotamine etc., and also gymnosperms like ephedra alkaloids.

11. DISTRIBUTION: Out of 60 different orders in higher plants, 34 orders contain alkaloids. Families with alkaloidal content are Apocynaceae,Berberidaceae,Euphorbiaceae,Leguminosae,Papaveraceae,Ranunculaceae,Rutaceae,Rubiaceae and Solanaceae In most of the plants alkaloids are highly localized and concentrated in certain morphological parts only.

12. Examples: All Parts e.g. Datura . Barks e.g. Cinchona,kurchi Seeds e.g. Nux vomica , areca, physostigma Roots e.g. Aconite , rauwolfia Fruits e.g. Black pepper, conicum Leaves e.g. Tobacco, coca, lobelia Latex e.g. Opium

13. PROPERTIES OF ALKALOIDS: Mostly all alkaloids are colourless, crystalline solids Sharp melting point Bitter taste Some alkaloids are coloured in nature, e.g. Berberine is yellow

14. Soluble in organic non-polar, immiscible solvents. The alkaloids containing quaternary bases are only water soluble. Some of the pseudoalkaloids and protoalkaloids shows higher solubility in water.

15. Some alkaloids are liquid because of lacking of oxygen in their molecules. ( e.g coniine, nicotine, spartenine ) Alkaloids are decomposed by heat, except Strychnine and caffeine. Give a precipitate with heavy metal iodides.

16. CLASSIFICATION: The various methods proposed for classification of alkaloids are explained as follows, 1. Pharmacological classification 2. Taxonomic classification 3. Biosynthetic classification 4. Chemical classification

17. PHARMACOLOGICAL CLASSIFICATION: Depending on the physiological response, the alkaloids are classified under various pharmacological categories, like central nervous system stimulants or depressants, analgesics , purgatives etc. Some of the examples are explained as follows,

18. Narcotic analgesic e.g.Morphine Antimalarial e.g. Quinine Reflux excitability e.g.Strychnine Respiratory stimulant e.g.Lobeline Neuralgia e.g. Aconitine Oxytoxic e.g. Erogotometrine Bronchodilator e.g. Ephedrine, vasicine Anticholinergic e.g. Atropine

19. CNS stimulant e.g. Caffeine Antitussive e.g. Codeine Antiarrythmic e.g.Quinidine Antihypertensive e.g. Reserpine Anticancer e.g. Vincristine Antiglucoma e.g. Pilocarpine

20. TAXONOMIC CLASSIFICATION: This method classifies vast number of alkaloids based on their distribution in various plant families, like solanaceous or papillionaceous alkaloids. From this classification, the chemotaxonomic classification has been further derived.

21. BIOSYNTHETIC CLASSIFICATION: This method give significance to the precursor from which the alkaloids are biosynthesized in plants. The alkaloidal drugs are categorised on the fact whether they are derived from amino acid precursor as ornithine , lysine, tyrosine, tryptophan, phenylalanine etc.

22. 1. Ornithine derived alkaloids e.g. Pyrrolidine alkaloid- Nicotine Tropane alkaloid - Atropine, hyosyamine , coacaine 2. Lysine derived alkaloids e.g. Piperidine and pyridine alkaloid - conine , lobaline , arecoline Quinazolidine alkaloid- lupinine 3 . Tyrosine derived alkaloids e.g. Isoquinoline alkaloid - Morphine, codeine, emetine, cephaline , berberine,d - tubocurine Amino alkaloid- colchicine

23. 4 . Tryptophan derived alkaloids e.g . Indole alkaloid- ergot alkaloid, vincristine , vinblastine , reserpine , strychnine, physostigmine , strychinine , brucine Quinoline alkaloid - cinchonine , quinine. 5 . Histidine derived alkaloids e.g. Imidazole alkaloid - Pilocrpine 6 . Phenylalanine derived alkaloids e.g. Amino alkaloid- Ephedrine

24. CHEMICAL CLASSIFICATION: This is the most accepted way of classification of alkaloids. The main criterion for chemical classification is the type of fundamental (normal heterocyclic) ring structure present in alkaloid. The alkaloidal drug care broadly categorised into 2 divisions.

25. (a) Heterocyclic alkaloids (True alkaloids) are divided into 12 groups according to nature of their heterocyclic ring. (b)Non- heterocyclic alkaloids or protoalkaloids or Biological amines or pseudoalkaloids . The following chart indicates types of alkaloids and their occurence in various plants alongwith basic chemical ring.

26. ISOLATION OF ALKALOID : Plant material is dried at a temperature not exceeding 60 ˚c and finely powdered. Macerate the powdered material with sufficient quantity of ethanol and set aside over night. Most alkaloids and their salts being alcohol soluble will get dissolved in the solution. Filter and concentrate the extract to ¼ the initial volume. complete the evaporation of the remaining solvent at a temperature not exceeding 50˚c.

27. Treat the residue with dil.sulphuric acid and filter to remove resins, fatty matter and other unwanted substances. Basify the solution by the addition of alkali such as ammonia as it effectively precipitates most alkaloids and because of its volatility. Extract this solution with succesive portion of chloroform or till complete extraction of all the alkaloids is effected.

28. Concentrate the pooled organic layer to yield a crude mixture of alkaloids of the plant material. Dissolve the above residue in dil.sulphuric acid and filter if necessary. Basify the solution with ammonia and successively extract with chloroform.

29. 10. Run the pooled chloroform layers through a bed of anhydrous sodium sulphate and evaporate to dryness .Note the weight of the mixture of total alkaloids.

30. QUALITATIVE CHEMICAL TEST: Wagner’s Test (+) Reddish brown precipitate Reagent used: Wagner’s Reagent [Solution of iodine in potassium iodide] Mayer’s Test (+) Cream color precipitates Reagent used: Mayer’s Reagent [Potassium mercuric iodide solution]

31. Dragendorff’s test (+) Orange precipitate Reagent used: Dragendorff’s reagent [Potassium bismuth iodide solution] Hager's test (+) Yellow color precipitate Reagent used: Hager's reagent [saturated solution of Picric acid]

32. Tannic acid test (+)buff color precipitate Reagent used: 10% Tannic acid solution

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