Alkaloids

1. Alkaloids Syllabus: Alkaloids: The details of the followings:Biosynthesis of tropane, quinoline, isoquinoline and indole alkaloids. i) Tropane-Belladona, stramonium, hyoscyamus and Cocaii) Quinoline-Cinchona, Cusparia barkiii) Isoquinoline-Ipecacs, Opium, sanguinaria, curareiv) Indole-Rawolfia, Nux vomica, Ergot, Catharanthusv) Imidazole: Pilocarpinevi) Steroidal: Veretrum viride, aconitevii) Lupinea-Lupinus sppviii) Purine base-Coffee, tea.

2. Alkaloids Alkaloids are basic nitrogenous compounds which occur abundantly in the plant kingdom. They contain one or more nitrogen atoms, usually in a heterocyclic ring and have a marked physiological action on man and animals. The nitrogen atom may exist as a primary amine (RNH2), as a secondary amine (R2NH) or as a tertiary amine (R3NH). These compounds are basic but the degree of basicity depends on the structure of the molecule and the presence and location of other functional groups.

3. Nicotine Atropine

4. Functions of alkaloids in plants • The possible functions of alkaloids in plants are • They are poisonous agents that protect • the plants against insect and herbivores. • Alkaloids are reserve substances capable • of supplying nitrogen or other necessary elements to the plants. • They are regulatory growth factors. • Alkaloids are the end product of detoxification reaction representing a metabolic locking up of compounds otherwise harmful to the plant.

5. Properties of alkaloids • Most alkaloids are well defined crystalline substances and unite with acids to form salts. In the plants they may exists in the free state or as salts. • The alkaloids are usually insoluble or sparingly soluble in water but their salts with acids are freely soluble. • The free alkaloids are soluble in ether, chloroform or other nonpolar solvents in which the alkaloidal salts are insoluble.

6. This property permits a ready means for the isolation and purification of alkaloids.The alkaloids usually possess a bitter taste

7. Pharmacological action The alkaloids have a wide range of pharmacological action. For example: Analgesic and narcotic morphine, codeine CNS stimulant strychnine Mydriatic atropine Myotic pilocarpine Hypertensive Ephedrine Antihypertensive Reserpine Antineoplastic vinblastine, vincristine Emetic emetine, sanguinarine Oxitocic ergonovine

8. Tests for alkaloids Most alkaloids are precipitated from neutral or slightly acid solution by various reagents. The precipitate may be amorphous or crystalline and are of various colors. Such as Reagent Color of ppt. Mayer’s reagentcream (Potassium mercuric iodide soln) Wagner’s reagentreddish brown (Soln of iodine in potassium iodide) Dragendorff’s reagent reddish brown (Soln of potassium bismuth iodide) Hager’s reagentyellow (Saturated solution of picric acid)

9. Classification Alkaloids may be classified in a number of ways. For example: they may be classified according to source, chemical structure, or pharmacological action. Each system has its own advantages and disadvantages.

10. Usually they are classified on the basis of ring structure or nucleus of the alkaloids as follows. • pyridine - piperidine group • tropane group • quinoline group • isoquinoline group • indole group • imidazole group • steroidal group • alkaloidal amine group • lupinane group • purine group

11. Pyridine - piperidine group The alkaloids in this group contain pyridine or piperidine in the molecule. The important alkaloids in this group are nicotine, coniine, arecoline, lobeline etc. pyridine piperidine Example: nicotine coniine

12. Tropane group Tropane is a dicyclic compound where both pyrroline and pipridine ring system are present. pyridine piperidinetropane Example: atropine

13. iii) Quinoline group Alkaloids containing the quinoline ring as the principal nucleus are quinine, quinidine, cinchonine and cinchonidine. Quinoline Example: quinine

14. iv) Isoquinoline group The isoquinoline ring occurs in a number of alkaloids in widely separated plant families. For example: papaverine, morphine, emetine etc. Quinoline Example: papaverine

15. v) Indole group A number of important alkaloids possess an indole ring in their structure. For example reserpine, vinblastine, vincristine, strychnine etc. Example: indole papaverine

16. vi) Imidazole group Imidazole ring occurs in the alkaloids pilocarpine, isopilocarpine etc. imidazole Example: pilocarpine

17. vii) Steroidal group The steroidal alkaloids are characterized by the cyclopentanoperhydrophenanthrene nucleus. The important alkaloids are protoveratrine A and B, Aconitine, conessine etc. Example: Cyclopenteno-perhydro-phenanthrene conessine

18. viii) Lupinane group The alkaloids in this group contain a dicyclic lupinane ring. For example , sparteine, lupinine etc. lupinane Example: lupinine

19. ix) Alkaloidal amine group The alkaloids in this group do not contain heterocyclic nitrogen atoms. For example, colchicine. Some are simple derivative of phenylalanine like ephedrine, mescaline etc. Example: colchicine phenylethylamine ephedrine

20. x) Purine group The alkaloids in this group contain a dicyclic purine ring. The important alkaloid in this group are caffeine, theobromine etc. purine Example: caffeine

21. Biosynthesis of tropane alkaloid

22. Tropane alkaloids:Tropane is a dicyclic compound where both Pyrrolidine and Piperidine ring systems are present. The important alkaloids in this group are Atropine, Hyoscyamine, Hyoscine (scopolamine) etc.

23. Biosynthesis of Tropane alkaloids: Tropane is formed by the condensation of Pyrrolidine compound with 3 acetate derived carbon atoms. The Pyrrolidine ring is formed from amino acid ornithine. The remaining 3 carbon atoms are derived from acetate and methylation results in the completion of the tropine nucleus. The 3-hydroxy derivative of tropane is called tropine. On the other hand from phenylalanine tropic acid is formed via rearrangement and other reactions. Esterification of tropine and tropic acid results in the formation of Hyoscyamine and thus other Tropane alkaloids are synthesized.

26. 1. Belladona 2. Stramonium3.Hyoscyamus 4. Coca Tropane alkaloid Containing plants-

27. Belladonna/ deadly nightshade: Biological source: Belladonna leaf consists of dried leaf and flowering or fruiting tops of Atropa belladonna Linne or its variety acuminata of Solanaceae family.

28. Belladonna root consists of dried roots of Atropa belladonna Linne of Solanaceae family.The plant is a perennial herb that grows to 1m in height. “Atropa” is from greek “atropos” meaning inflexible. Atropos is the name of Greek Fate who cuts the thread of life and probably refers to the poisonous character of the drug. “Belladonna” is from two Italian words “bella” meaning beautiful and “donna” meaning lady. This probably refers to the fact that, juice of the berry of plant when placed in the eyes causes dilation of the pupils giving an outstanding appearance.

29. Geographical source: It is indigenous to central and southern Europe and to Asia Minor and is cultivated in sunny locations in England, Germany, India and USA. But the chief supply comes from Balkans. Constituents: Belladonna leaf yields about 0.4% (no less than 0.35%) and belladonna root yields about 0.6% alkaloids containing About of the mixture is Hyoscyamine Remaining is atropine Use: As Mydriatics, As parasympatholytic agent (depress or block parasympathetic nerve). Thus it decreases the flow of most secretions like saliva, sweat, milk, gastric secretion etc. Thus it is used as adjunct therapy in peptic ulcer and different GIT disorders.

30. Stramonium/thorn apple/jimson weed/Jamestown weed: Biological source: It consists of dried leaf and flowering or fruiting tops (with branches) of Datura stramonium Linne or its variety Tatula Torrey of Solanaceae family. The plant is an annual herb that attains height of about 2m.

31. Geographical source: Datura stramonium grows wild in most tropical countries including Bangladesh and India and cultivated in Spain, France, Germany and Hungary. It is indigenous to the region of Caspian Sea. It occurs naturally in waste places of Europe and North America. It is cultivated in Central Europe and South America specially Argentina. Constituents: The drug contains 0.2-0.4% alkaloids (it yields no less than 0.25% if ideal). The alkaloids present are Tropane alkaloids Hyoscyamine. This is more abundant. Use: Its actions are similar to belladonna. It is used as Parasympatholytic Anticholinergic It is used in preparations intended to burn to yield vapor that relief asthma.

32. Hyoscyamus/henbane: Biological source: Hyoscyamus or henbane is the dried leaf with or without the flowering or fruiting top of Hyoscyamus niger Linne of Solanaceae family.The plant is an annual or biennial herb.

33. Geographical source: The plant is indigenous to Europe, western Asia and northern Africa. It is cultivated in the Soviet Union, the Balkans, Belgium, England and Germany as well as USA and Canada. Constituents: The drug contains about 0.05-0.15% alkaloids (no less than 0.04%). Alkaloids include Use: As parasympatholytic but its use is as crude drug in medicine is rare.[Egyptian henbane (Hyoscyamus muticus) yields about 1.5% alkaloids most of which is Hyoscyamine]

34. Coca/coca leaf: Biological source: It is the dried leaves of Erythroxylum coca Lamack (Huanuco coca) or E. truxillence Rusby(Truxillo coca) of Erythroxylaceae family.

35. The plant is a shrub or small tree attaining a height of about 2m.There are several varieties Huanuco coca Truxillense coca Colombian coca Geographical source: The plant is indigenous to some areas of South America and cultivated in Bolivia, Peru, Colombia, Indonesia and Sri Lanka.

36. Constituents: Coca contains three basic types of alkaloids Derivatives of ecgonine Derivatives of tropine Derivatives of hygrine With different variety the composition of alkaloid mixture varies. But cocaine is the major alkaloid. Cocaine is the methyl ester of benzoyl ecgonine. When hydrolyzed it splits into ecgonine, benzoic acid and methyl alcohol. Huanuco coca yields about 0.5-1% of alkaloids whereas Truxillense coca give lower amount but higher percentage of cocaine. Use: Cocaine and its hydrochloride salt are local anesthetic (applied as 1-4%). When taken internally it is CNS stimulant. When taken in larger dose or used continuously it becomes narcotic.

37. Biosynthesis of Quinoline alkaloid

38. Quinoline alkaloids: Alkaloids containing the Quinoline ring as the principal nucleus are Quinine, Quinidine, Cinchonine, Cinchonidine etc. Quinine

39. Biosynthesis of Quinoline alkaloids:The precursor of quinine and other Quinoline alkaloid is Tryptophan. Its biosynthesis in plant is not fully understood but in microorganisms it is obtained via shikimic acid pathway. In this pathway shikimic acid through a series of phosphorylation reaction yields chorismic acid. Chorismic acid is an important branch point where one branch leads to prephenic acid and then to aromatic amino acids like tyrosine, phenylalanine where the other branch lead to anthralinic acid and then to Tryptophan.Tryptophan and corynanthe like monoterpene form corynantheine which yield quinine.

43. 1. Cinchona2. Cuprea bark Quinoline alkaloid Containing plants-

44. Cinchona/Peruvian bark/cinchona bark: Biological source: It is the dried bark of the stem or the roots of Cinchona succirubra or its hybrids (red cinchona) and C. ledgeriana Moens et Trimen, C. calisaya Weddell or hybrids of these with other Cinchona species (yellow cinchona) of Rubiaceae family. The plant is a tall tree attaining 15-20m. Geographical source: It is indigenous to Ecuador and Peru. It is cultivated in India and Indonesia. The plant grows at elevation of 1000-3000 meters. The drug is cultivated in Netherlands and Germany from the bark obtained from elsewhere.

45. Constituents: Cinchona contains about 25 closely related alkaloids. The average yield is 6-7%. The alkaloids include Quinine Quinidine Cinchocine Cinchonidine In the red cinchona Cinchonidine exist in greater proportion (as much as 18%) whereas in yellow bark two third is quinine. Use: As febrifuge. Cinchona bark and its alkaloids have been used in the treatment of malaria fever for many years. Quinine is still used in malarial treatment in many parts of the world. Quinidine is cardiac depressant and used to prevent auricular (atrial) fibrillation to coordinate contraction of the auricular (atrial) muscle.

46. Cuprea bark: • Biological source: • Cuprea bark is obtained from Remijia purdieana Traina and R. pedunculata Fluckiger of Rubiaceae family. • The plant is a tree. • Geographical source: • The plant is indigenous to central and southern Colombia. • Constituent: • It yields about 2-6% alkaloids containing • one third quinine • Quinidine and cuprea bark is the major commercial scource of Quinidine. • Use: • Quinidine is used as cardiac depressant.

47. Isoquinoline alkaloids: The Isoquinoline ring occurs in a number of alkaloids in widely separated plant families. For example: Papaverine, Morphine, Emetine etc. Example:

48. Biosynthesis of Isoquinoline alkaloids

49. Biosynthesis of Isoquinoline alkaloids: From phenylalanine of tyrosine Phenylethylamine derivatives and phenylacetaldehyde derivatives are obtained which are condensed to give Isoquinoline alkaloids. Morphine (and codeine, thebaine) is also formed from tyrosine (2 molecules) and in the biosynthetic pathway Norlaudanosoline is a key intermediate.

50. Biosynthesis of Isoquinoline alkaloids: