Alkaloids

Full information of Alkaloids

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

2. 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

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

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

5. TESTS FOR ALKALOIDS Most alkaloids are precipitated from neutral or slightly acidic solution by D ragendorff's reagent (solution of potassium bismuth iodide)orange coloured precipitate. M ayer's reagent ( potassio mercuric iodide solution) Cream coloured precipitate. W agner’s reagent (iodine in potassium iodide) red-brown precipitate H agers reagent (picric acid) yellow precipitate Caffeine does precipitate Mr.Vishal S Bagul Department of Pharmacognosy,RCPIPER,Shipur

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

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

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

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

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

11. NAMING OF ALKALOIDS Numerous methods can be used to name alkaloids 1-Generic plant name –atropine from Atropa belladonna 2-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 emesis 5-Other –e.g. morphine derived from ancient Greek mythology –Morpheus –god of dreams Mr.Vishal S Bagul Department of Pharmacognosy,RCPIPER,Shipur

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

13. 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

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

15. 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

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

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

18. Classification of Alkaloids 1. Biological origin Sedatives : Morphine Vasodilatation : Ephedrine, Ergonovine . Local anesthetic : Cocaine Hallucinating : Mescaline , Psilocybin . Mr.Vishal S Bagul Department of Pharmacognosy,RCPIPER,Shipur

19. 2-Biosynthetic pathway Ornithine- Tropane , Pyrrolidine , Pyrrolizidine Tyrosine- Benzyl isoquinoline Tryptophane - Indole alkaloids, Quinoline Pyridine- Pyridine Lysine- Quinolizidine , Piperidine Mr.Vishal S Bagul Department of Pharmacognosy,RCPIPER,Shipur

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

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

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

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

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

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

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

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

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

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

30. Biosynthetic classification 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 4. Tryptophan derived alkaloids e.g . Indole alkaloid- ergot alkaloid, vincristine , vinblastine , reserpine , strychnine, physostigmine , strychinine , brucine Quinoline alkaloid – cinchonine , quinine, quinidine , camptothecin 5. Histidine derived alkaloids e.g. Imidazole alkaloid – Pilocrpine 6. Phenylalanine derived alkaloids e.g. Amino alkaloid- Ephedrine Mr.Vishal S Bagul Department of Pharmacognosy,RCPIPER,Shipur

31. Pharmacological classification Narcotic analgesic e.g.Morphine Antimalerial e.g. Quinine Reflux excitability e.g.Strychnine Respiratory stimulant e.g.Lobeline Neuralgia e.g. Aconitine Oxytocic e.g. Erogotometrine Bronchodilator e.g. Ephedrine, vasicine Anticholinergic e.g. Atropine 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 Mr.Vishal S Bagul Department of Pharmacognosy,RCPIPER,Shipur

32. Biosynthesis of indole alkaloids Mr.Vishal S Bagul Department of Pharmacognosy,RCPIPER,Shipur

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

34. Biosynthesis of Isoquinoline alkaloids Mr.Vishal S Bagul Department of Pharmacognosy,RCPIPER,Shipur

35. Biosynthesis of Tropane alkaloids Mr.Vishal S Bagul Department of Pharmacognosy,RCPIPER,Shipur

36. Biosynthesis of Quinoline alkaloids Mr.Vishal S Bagul Department of Pharmacognosy,RCPIPER,Shipur

37. Thank You…