Alkaloids.pptx

Alkaloids presented by Dhanashree Kavhale M.Pharm. I semester (Pharmaceutical Chemistry)
Alkaloids are secondary metabolites produced by plants in a unique pattern.

1. Alkaloids

2. Introduction of Alkaloids Alkaloids are secondary metabolites produced by plants in a unique pattern. Alkaloid term was coined by W. Meissner in 1819. ( Pflanzenkalien ) Alkaloids were defined as a basic nitrogen compound isolated from plants and contain at least one nitrogen atom in heterocyclic ring. Alkaloids are the “basic nitrogenous plant products mostly optically active and possessing nitrogen heterocycles as their structural units, with a pronounced pharmacological activity.” exceptions: Colchicine(non heterocyclic) Thiamine (heterocyclic) 2

3. Nitrogen: 1. cyclic / heterocyclic : True alkaloids 2. Acyclic : Amino alkaloids 3. Absence of N : Pseudo Alkaloids Occurrence of Alkaloids: Free base : Amorphous , Organic Non-polar solubility Salt form : Crystalline , Polar Solubility Properties of Alkaloids: Colourless except berberine (yellow), betanidine and Sanguinarine (red). mostly solids , non volatile except conine, nicotine, sparteine. Optically active except Papaverine. Bitter in taste. 3

4. Chemical Tests 1. Mayer’s Reagent : Potassium Mercuric Iodide - Cream Precipitate. 2 . Dragandorff’s Reagent : Potassium Bismuth Iodide – Reddish brown Precipitate. 3. Wagner’s Reagent : Potassium Iodide + Iodine – Red Precipitate. 4. Hager’s Reagent : Picric acid – Yellow coloured Precipitate. 5. Picrolonic acid Test : Solution of picrolonic acid- Yellow color . 4

5. Classification Taxonomical classification: based on the distribution of alkaloids in various plant families, genus. Biosynthetic classification: gives significance to the precursor from which the alkaloids are biosynthesized. Pharmacological classification: Based on the physiological action or biological activity of alkaloids on animals. Chemical classification: This classification is most accepted way to specify the alkaloids. 5

6. Chemical classification Tropane Alkaloids: Atropine Pyrrole and Pyrrolidine: Nicotine Pyridine and Piperidine: pilocarpine Pyrrolizidine: Echimidine Quinoline: Quinine, quinidine Isoquinoline: Morphine Indole: reserpine, vincristine Imidazole: Pilocarpine, pilosine Norlupinane: spartaine Purine: Caffeine, Steroidal: Solasodine, solanine Diterpene: Aconitine Amino alkaloid: Ephedrine 6

7. Isolation Based on their basic character and solubility pattern. There are two methods : 1. stass otto method 2. Manske’s method stass otto method: Powder drug treated with the 90-95% ethanol. (proportion of crude drug to solvent 1:1 ) Distillation is done under vacuum – remove alcohol Aqueous residue treated with pet. Ether (60-80) – remove fatty cpd. if any alkaloid removed by pet. Ether, recovered by dil. Mineral acid. Resulting aq. Extract mixed with previous one. Extract filtered and then dried under vacuum. Residue extracted with ab. Ethanol, dissolving total alkaloid contents. 7

8. Purification 1. Direct crystallization from solvent: It is a simple method of isolation in which the alkaloids crystallize directly by fractionation process. May not be useful in case of complex mixtures. 2. Steam distillation: Used for volatile liquid alkaloids like coniine, sparteine and nicotine. Not suitable for alkaloids of high molecular weights . In this method, the aqueous extract is made alkaline with caustic soda or sodium carbonate and then alkaloids are distilled off in steam. 8

9. 3. Gradient pH technique: The crude alkaloid mixture is dissolved in 2% tartaric acid, extracted with benzene. first fraction very weakly basic alkaloids. The pH value of the aqueous solution is increased gradually by 0.5 increments to pH 9 and extraction is carried out at each pH. By this way, the alkaloids of different basicity are extracted and strongly basic alkaloids extracted at the end. 4. Chromatographic techniques: The separation of alkaloids carried out by using stationary and mobile phase of different organic solvents. The different techniques of chromatography used for separation of individual alkaloid from complex mixture. 9

10. Biological activity of Alkaloids In Plants They may act as protective against insects and herbivorous due to their taste and toxicity. They are in certain cases the final products of detoxification. Source of nitrogen in case of nitrogen deficiency. They may be utilized as a source of energy in case of deficiency in carbon dioxide assimilation. 10

11. In humans Shows high biological activity. Produce various degrees of physiological and psychological responses by interfering neurotransmitter,. Large dose shows highly toxic fatal Small dose may have therapeutic value. Muscle relaxant, pain killers, tranquillizers, mind altering drugs, chemotherapy. 11

12. General methods of structural determination of alkaloids Molecular formula Determination Functional group analysis Functional Nature of oxygen Nature of Nitrogen Estimation of C- methyl group Degradation of alkaloids Physical methods 12

13. Molecular Formula : The first step in structural elucidation is the determination of molecular formula and optical rotatory power. Elemental composition and hence the empirical formula is found by combustion analysis. Determination of Unsaturation: The unsaturation can be determined by adding bromine, halogen acids or by hydroxylation with KMnO4 or by reduction (using either LiAlH4 or NaBH4 ). Functional Group Determination: By using the usual standard chemical tests or by infrared (IR) spectroscopy. 13

14. Hydroxyl group: By determining the amount of Acetic anhydride /Acetyl chloride or benzoate that reacted with alcohol to form an ester, the number of hydroxyl groups can be determined. Nature of Nitrogen: General reactions of alkaloids with acetic acid, methyl iodide and nitrous acid indicates the nature of nitrogen. If all reactions are negative – N2 probably tertiary Majority of nitrogen presence in alkaloids are secondary and tertiary: If tertiary when treated with H2O2 (30%) form amine oxide. Herzig- Mayer method: presence and number of N- methyl group Nature and No. alkyl group attached to Nitrogen: Distillation with Aq. KOH, formation of methylamine, dimethylamine and trimethylamine. 14

15. Degradation of alkaloids: Study of degradation of alkaloids gives rise to some identifiable products of known structure. Knowing structure of the degraded products and the changes occurred during the degradation, it is convenient to know the structure of the original molecule. Different degradation reactions Hoffman exhaustive methylation method Emde’s method Von Braun’s (VB) method for 3° cyclic amines Reductive degradation Oxidation Zinc distillation Alkali fusion Dehydrogenation 15

16. Physical method: Development of physical method has revolutionized the structural elucidation of complex alkaloids. It has advantage over time consuming methods like degradation. Extensive methods are replaced by spectral analysis of compound Important physical techniques for determination are: 1.NMR spectroscopy 2. Mass spectrometry 3. UV-Vis spectroscopy 4. I.R. spectroscopy 16

17. Reference Chemistry of Natural products,VOLUME-1.,O.P.AGARWAL 17

18. Thank you ! 18