Chemical analysis of MPM that contain alkaloids

1. Chemical analysis of MPM that contain alkaloids

2. Alkaloids are complex organic compounds of basic nature containing nitrogen. They are vegetable origin (seldom animal origin) and have very strange, specific physiological effect on the body. The name “alkaloid” is derived from Arabian olkali – alkali and Greek eidos – similar to alkali.

3. Typical alkaloids are derived from plant sources. they are basic. They contain one or more nitrogen atoms(usually in a heterocyclic ring) and they usually have a marked physiological action on man or other animals Some 150 years of alkaloid chemistry had resulted by the mid-1940s in the isolation of about 800 alkaloids: the new technology of the next years increased this figure to the order of 10 000.

4. Classification • BIOGENETIC CLASSIFICATION • Alkaloids are usually classified according to the nature of their chemical structure: • Protoalkaloids • True alkaloids • Pseudoalkaloids • 1. Ephedrine

5. 2. Chemical classification (suggested by Oryekhov)– alkaloids are divided into groups accoring to nitrogen bearing heterocycle. There are: • Pyrolydine derivatives • Pyperidine derivatives • Pyridine derivatives • Pyrolysidine derivatives • Quinolysidine derivatives • Quinoline derivatives • Isoquinoline derivatives • Indole derivatives • Imidazole derivatives • Acridine derivatives • Purine derivatives • Tropane derivatives

6. Pyrolydine Pyrolysidine Tropane Indole Imidazo le Purine Pyperidine Pyridi ne Quinoline Isoquinoline Quinolysidine Acridine

7. 3. “Pseudoalkaloid” has been introduced to cover alkaloids, which are formed from terpenes: 1) Terpenoid alkaloids. They are monoterpenes, sesquiterpenes and diterpenes (e.g. Alkaloids of Aconitum, Delphinium and Taxus). Aconitine

8. 2) Steroidal alkaloids are characterised by the cyclopentenoperhydrophenanthrene nucleus. Solasodine, veratrum, alkamine esters and their glycoside are the main alkaloids of this group. They occur in genus: Solanum, Veratrum. Solasodine

9. II. Phylogenetic or botanical classification (on a close botanical and chemical affinity) All isolated alkaloids from plants from the same family or genus are combined (ipecacuanha alkaloids, colchicine alkaloids, etc.).

10. III. Pharmacological classification Pharmacological classification divides alkaloids according to its pharmacological effects on: narcotic analgesics, sympatholytic means, alkaloids that inhibit the cough center, etc.

11. IV. Biosynthetic classification combines alkaloids according to the name of amino acids (precursors) from which they are synthesized. Ornithine - pyrrolidine, pyrrolizidine, tropane some pyridine alkaloids derivatives.Lysine – Quinolizine and some piperidine alkaloidsTyrosine - isoquinoline alkaloidsTryptophan - indole, quinoline, pyridine and some piperidine alkaloidsHistidine - imidazole alkaloids such as pilocarpineGlycine and aspartic acid - purine alkaloids

12. Medical plant materials containing alkaloids storage according the list B. But Nux vomica seeds (Strychni semen), Colchicum corm (Colchici bulbotubera recens), Scopoliae carniolicae rhizomata - the list A.

13. Biosynthesis Asometine (Schiff base) N-hydtoximethilic derivate CH-acidic component Acid amide Condensation product

14. Alkaloids accumulate in 4 types of tissues:1) those that are actively growing;2) in epidermal and hipodermal;3) in the facing of vascular bundles;4) in latex vessels

15. Properties Most alkaloidsa are well-defined crystalline substances which unite with acids to form salts. In the plant they may exist in the free state, as salts or as N-oxides (see below). ln addition to the elements carbon, hydrogen and nitrogen, most alkaloids contain oxvgen. A f'ew, such as coniine from hemlock and nicotine from tobacco, are oxygen-free and are liquids. Although coloured alkaloids are relatively rare, they are not unknown; berberine, for example is yellow and the salts of sanguinarine are copper-red.

16. A knowledge of the solubility of alkaloids and their salts is considerable pharmaceutical importance. Not only are alkaloidal substances often administered in solution, but also the differences in solubility between alkaloids and their salts provide methods for the isolation of alkaloids from the plant and their separation from the nonalkaloidal substances also present. While the solubilities of different alkaloids and salts show considerable variation, as might be expected from their extremely varied structure, it is true to say that the free bases are frequently sparingly soluble in water but soluble in organic solvents; with salts the reverse is often the case, these being usually soluble in water but sparingly soluble in organic solvents. For example, strychnine hydrochloride is much more soluble in water than is strychnine base.

17. It will soon be realized that there are many exceptions to the above generalizations, caffeine (base) being readily extracted from tea with water and colchicine being soluble in either acid, neutral or alkaline water. Again, some alkaioidal salts are sparingly soluble-for example. quinine sulphate is only soluble to the extent of 1 part in 1000 parts of water, although 1 part quinine hydrochloride is soluble in less than 1 part of water.

18. General precipitate reactoins on alkaloids • With Major’s reagents (bichloride mercury solution on potassium iodide solution) – white or yellow precipitate. • With Vagner’s and Bushard’s reagents (iodine solution in potassium iodide) – brown precipitates that are the compounds of alkaloids hydroiodides with iodine. • With Drehendorf’s reagent (bismuth subnitrate solution potassium iodide and acetic acid) – orange-red or brick-red sediment. • With Marmer’s reagent (cadmium iodide solution in potassium iodide) – white or yellowish sediment, often soluble in surplus reagent.

19. With tannin solution – whitish or yellowish amorphic precipitate. • With picric acid solution – yellow precipitate. • With Zonnenshtein’s reagent (phosphoromolybdenic acid) – yellowish amorphic precipitate, getting dark-blue or green colour. • With silicon tugsten acid – whitish precipitate.

20. The most sensative reagent on alkaloids is a modified Dragendorif's reagent. Caffeine and some other alkaloids do not give these precipitate. Care must be taken in the application of these alkaloidal tests, as the reagents also give precipitates with proteins. During the extraction of alkaloids from the plant and subsequent evaporation, some proteins will not be extracted and others will be made insoluble( denatured) by the evaporation process and may be filtered out.

21. Extraction of alkaloids Process A. The powdered material is moistened with water and mixed with lime which combines dilute acids, tannins and other phenolic substances and sets free the alkaloids (if they exist in the plant as salts). Extraction is then carried out with organic solvents such as ether or petroleum spirit. The concentrated organic liquid is then shaken with aqueous acid and allowed to separate. Alkaloid salts are now in the Aqueous liquid, while many impurities remain behind in the organic liquid. Process B. The powdered material is extracted with water or aqueous alcohol containing dilute acid. Pigments and other unwanted materials are removed by shaking with chloroform or other organic solvents. The free alkaloids are then precipitated by the addition of excess sodium bicarbonate or ammonia and separated by filtration or by extraction with organic solvents.

22. Biological Effect and Application of Alkaloids Alkaloid-bearing plants are used in Pharmacy and Medicine with different purposes. They are used directly at the Chemist’s shops for manufacturing of extracts and decoctions (thermopsis – Thermopsis Lanceolata). The others are used for manufacturing galenicals tinctures, extracts, neogalenicals. Alkaloids are produced from raw stuff in pure form and then manufactured as: tablets, ampoules, drage. Medical significance of alkaloids: • analgetics (Poppy remedies) • hemostatics (Claviceps purpurea medicines ) • cardiovascular remedies (ephedra) • anticancer (autumn crocus remedies ) • spasmolytic (beladonna). It is not possible to describe all types of phamacological effects. Effects of some alkaloids on the human body are studied well. These substances effect on specific receptors or influence enzyme activity.