1. Alkaloids

2. Definition Alkaloids are basic nitrogen containing compounds. They are generally obtained from plants, animals and microorganisms and often demonstrate a marked physiological action 3. 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 . 4. 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. Wagners reagent (iodine in potassium iodide) red-brown precipitate Hagers reagent (picric acid) yellow precipitate Caffeine does precipitate 5. 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 6. 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) 7. 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 8. 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. 9. 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 10. 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. 11. 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 12. 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. 13. 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 Mayers reaction on the aqueous phase becomes negative). This purification step may be carried out in a separation funnel or in centrifugal 14. 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. 15. 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) 16. Classification of Alkaloids 1. Biological origin Sedatives : Morphine Vasodilatation : Ephedrine, Ergonovine . Local anesthetic : Cocaine Hallucinating : Mescaline, Psilocybin. 17. 2-Biosynthetic pathway Ornithine- Tropane, Pyrrolidine, Pyrrolizidine Tyrosine-Benzyl isoquinoline Tryptophane- Indole alkaloids, Quinoline Pyridine- Pyridine Lysine- Quinolizidine, Piperidine 18. 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. 19. 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: 20. Name Structure Biological Significance Ephedrine Adrenergic agent- used for asthma and hay fever Colchicine Relieves gout Erythromycin Antibiotic 21. Taxol (Paclitaxel) Used in the treatment of ovarian cancer, breast cancer and non-small cell lung cancer 22. 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 23. No. Heterocycle Example 1. Pyrrole and Pyrrolidine Hygrine, Stachydrine 2. Pyrrolizidine Senecionine, Symphitine, Echimidine, Seneciphylline 24. 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 25. 6. Isoquinoline Morphine, Emetine, Papaverine, Narcotine, Tubocurarine, Codeine 7. Aporphine (reduced isoquinoline/naphthalene) Boldine 8. Quinolizidine Lupanine, Cytisine, Laburnine, Sparteine 26. 9. Indole or Benzopyrole Ergometrine, Vinblastine, Vincristine, Strychnine, Brucine, Ergotamine, Yohimbine, Reserpine, Serpentine, Physostigmine 10. Indolizidine Castanospermine, Swainsonine 11. Imidazole or glyoxaline Pilocarpine, Pilosine 27. 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.