Pharmacognosy II. Alkaloids

Transcription

1 Pharmacognosy II Alkaloids

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3 A significant contribu/on to the chemistry of alkaloids in the early years of its development was made by the French researchers Pierre Joseph Pelle/er and Joseph Bienaime Caventou, who discovered quinine (1820) and strychnine (1818). Several other alkaloids were discovered around that /me, including xanthine (1817), atropine (1819), caffeine (1820), coniine (1827), nico/ne (1828), and cocaine (1860).

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5 Distribu/on and occurrence Rare in lower plants. Dicots are more rich in alkaloids than Monocots. Families rich in Alkaloids: Apocynaceae, Rubiaceae, Solanaceae and Papaveracea. Families free from Alkaloids: Rosaceae, Labiatae

6 Distribu/on in Plant All Parts e.g. Datura. Barks e.g. Cinchona Seeds e.g. Nux vomica Fruits e.g. Black pepper Latex e.g. Opium Leaves e.g. Tobacco

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8 Physical Proper/es I- Condi/on: Most alkaloids are crystalline solids. Few alkaloids are amorphous solids e.g. eme:ne. Some are liquids that are either: Vola/le e.g. nico:ne and coniine, or Non-vola/le e.g. pilocarpine and hyoscine. II- Color: The majority of alkaloids are colorless but some are colored e.g.: Colchicine and berberine are yellow. Canadine is orange. The salts of sanguinarine are copper-red.

9 Physical Proper/es III- Solubility: Both alkaloidal bases and their salts are soluble in alcohol. Generally, the bases are soluble in organic solvents and insoluble in water Excep/ons: Bases soluble in water: caffeine, ephedrine, codeine, colchicine, pilocarpine and quaternary ammonium bases. Bases insoluble or sparingly soluble in certain organic solvents: morphine in ether, theobromine and theophylline in benzene. Salts are usually soluble in water and, insoluble or sparingly soluble in organic solvents.

10 Chemical Proper/es 1- Nitrogen: Primary amines (R-NH 2 ) e.g. Norephedrine Secondary amines(r 2 -NH) e.g. Ephedrine Ter/ary amines (R 3 -N) e.g. Atropine 2- Basicity: R 2 -NH > R-NH 2 > R 3 -N

11 According to basicity Alkaloids are classified into: Weak bases: e.g. Caffeine Strong bases: e.g. Atropine Neutral alkaloids: e.g. Colchicine

12 3- Oxygen: Most alkaloids contain Oxygen and are solid in nature e.g. Atropine. Some alkaloids are free from Oxygen and are mostly liquids e.g. Nico/ne, Coniine. 4- Stability: Effect of heat: Alkaloids are decomposed by heat, except Strychnine and caffeine. Reac/on with acids: 1- Salt forma/on. 2- Dilute acids hydrolyze Ester Alkaloids e.g. Atropine

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18 Classifica:on of Alkaloids N H N N H Piperidine Pyridine Pyrrolidine Tropane Quinoline Me N N N NH N H N NH N N N NH Isoquinoline Tetrahydroisoquinoline Indole Imidazole Purine

19 Classification of alkaloids depending on chemical structure 1) derivatives of pyrrolidine (sthrahidrine, turicine) 2) derivatives of tropane (atropine, cocaine) 3) derivatives of pyperidine (lobeline, coniine) 4) derivatives of pyridine (nicotine, anabasine) 5) derivatives of pyrrolysidine (platyphylline) 6) derivatives of quinolysidine (pahicarpine, lupinine) 7) derivatives of quinoline (quinine) 8) derivatives of isoquinoline (papaverine, morphine) 9) derivatives of indol (reserpine, strychnine) 10) derivatives of purine (caffeine, theobromine, theophylline)

20 11) derivatives of the different heterocycles (imidazol (pilocarpine), thiazol (agroheline), quinazoline (luotoline А), acridine (rutacridone), azenine (galantamine)); 12) polypeptide alkaloids (13-, 14-, і 15-member) (buckthorn alkaloids); 13) alkaloids with exocyclic nitrogen atom (ephedrine, muscarine, spherophysine); 14) terpenoid alkaloids (acronicyne, actinidine); 15) steroid alkaloids (solasodine, cholophyllamine).

21 Depending on biosynthesis pathways (according to the substances from which they are obtained): a) true alkaloids (1-12 group) which is synthezed from aminoacids and heterocycles are the base of their structure; b) protoalkaloids (13 group) do not include heterocycles, also are the plant amines and formed from aminoacids; c) pseudoalkaloids (14, 15 group) obtained by others ways different from aminoacids.

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28 Methods of extraction from plant materials extraction in the form of salts (water, alcohol, tartaric acid); extraction in the form of basis (NH 4 OH, NaHCO 3 ); Distillation of alkaloids bases with aqueous steam (boiling point for which is less than 100 º C).

29 Extraction as salts: to raw material add water or ethanol with few drops of tartaric acid. All alkaloids forms salts with tartaric acid. For purification to this extract add base and all alkaloids form bases, which obtained by organic solutions. Operation of purification repeat few times. Then solvent separated from alkaloids. Sum of alkaloids is separated on individual compounds. Extraction as bases: to raw material add alkali solution (ammonium, sodium hydrocarbonate or carbonate). Alkaloids bases are extracted by organic solutions. Purification realize by transferring alkaloids to salts and then to bases. Operation of purification repeat few times.

30 The methods of separa/on of the selected amount of alkaloids: Fractional distillation in vacuum; By the different solubility of alkaloids salts and bases; By the different power of basic properties of alkaloids; based on the features of chemical properties; By the different ability to adsorption (chromatography); Method of anticurrent separation.

31 For identification of alkaloids use general, group and specific reaction. The general reactions conduct with common alkaloid precipitation and special reagents. General precipitate reactions based on the ability of alkaloids as bases to give simple or complex salt with different, more often complex acids, salts of heavy metals and others. These products are usually not soluble in water, so called precipitate.

32 Methods of the quan/ta/ve determina/on of alkaloids: Acid-base titration in nonaqueous environment for the quantitative determination of both salts and bases. Acid-base titration: а) acid-base titration, direct titration of acids and bases; b) acid-base back-titration for determination of bases by reverse titration; c) Alkalimetry titration of alkaloids salts by alkali in wateralcohol medium in the presence of phenolphthalein (with or without the usage of organic solvent that does not move with water for extraction of alkaloid bases) d) Alkalimetry by the substituent Gravimetric method Methods based on individual chemical properties of alkaloids. Physico-chemical methods.