5-Tropane_Akaloids_.pptx

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Solanaceous alkaloids
(Atropine, Hyoscyamine and Hyoscine).

Coca alkaloids
(Cocaine, Cinnamyl cocaine and α- and β-truxillines).

1. Phytochemistry Tropane Alkaloids Assoc. Prof. Dr. Mostafa Mahmoud Hegazy

2. content Solanaceous alkaloids (Atropine , Hyoscyamine and Hyoscine). Coca alkaloids (Cocaine , Cinnamyl cocaine and α- and β- truxillines ).

3. ALKALOIDS DERIVED FROM ORNITHINE AMINO ACID Tropane Alkaloids

4. Tropane Alkaloids Tropane is a bicyclic, 7-membered compound formed by the condensation of Pyrrolidine and Piperidine with one nitrogen atom.

5. ◘ Tropane nucleus is a seven carbon bicyclic ring . nitrogen bridge is between Carbons 1 and 5

6. ◘ Tropane alkaloids are ester alkaloids , formed by esterification of an alcoholic base with specific organic acid . ◘ Being esters , they are unstable towards acid and alkali and are thermolabile.

7. Alcoholic bases in Tropane Alkaloids

8. Esterifying acids in Tropane Alkaloids * Tropic acid ( a -phenyl- b -hydroxyl-propionic acid) * The optically active ( l -form ) occurs in Hyoscyamine and Hyoscine . * The optically inactive (Racemic mixture) [ dl-form ) occurs in Atropine

9. Esterifying acids in Tropane Alkaloids

10. Examples of Tropane alakloids 1) Solanaceous alkaloids e.g. Atropine, Hyoscyamine and Hyoscine . 2) Coca alkaloids e.g. Cocaine , Cinnamyl cocaine and α - and β - truxillines .

11. 1 ) Atropa belladonna ( Belladonna Leaves ). 2) Datura stramonium ( Thornapple ) . 3) Hyoscyamus niger ( European henbane ) 4) Hyoscyamus muticus ( Egyptian henbane ) SOLANACEOUS ALKALOIDS

12. Solanaceous Alkaloids During acid–base extraction, hyoscyamine tends to racaemise forming atropine i.e. (±)- hyoscyamine . Indeed , the benzylic chiral center in the tropic acid moiety can be epimerised by action of heat and bases ( Rosemblum and Taylor, 1955 ).

13. Number of atropine chiral center(s)? The ring is symmetric so all three carbon centers shown in are not chiral. The sole chiral center is the α-carbon to carbonyl group . Atropine is optically inactive due to intermolecular compensation (i.e. racemic modification).

14. Hyoscine Hyoscyamine Atropine ( dl- Hyoscyamine ) Is optically active, levorotatory ( l-form ) It is a syrupy liquid It has the same structure of Atropine but differs in having an optically active l-tropic acid moiety . It dose not occur naturally in the plant. It results from racemization of the naturally occurring l- Hyoscyamine during extraction. It hydrolyzed by dil. acid or alkali to yield l-tropic acid + Scopoline base It hydrolyzed by dil. Acid or alkali to yield l-tropic acid + tropine base It hydrolyzed by dil. Acid or alkali to yield dl-tropic acid + tropine base It converted to Atropine by keeping its alcoholic solution in the presence of dil. acid or alkali

15. Hyoscine Hyoscyamine Atropine ( - ) l ( - ) l (±) dl Optical activity. Naturally occurring. Naturally occurring. Not naturally occurring. Occurance Liquid. Solid. Solid. Condition l- tropic acid + scopoline base l- tropic acid + tropine base dl- tropic + tropine base Hydrolysis - Soluble . Insol. in Acetone: Ether (1:1) Oxalate Salt Weak base Strong base Strong base Basicity

16. USES of Atropine ◘ Atropine sulfate has an anti-cholinergic effect ( parasympatholytic activity ). ◘ A mydriatic ( causes dilatation of the eye pupil ). ◘ An antispasmodic ( relaxes the intestinal and bronchial smooth muscles ). ◘ A preanesthetic medication to stop body secretions. ◘ A CNS stimulant. ◘ An antidote to organophosphorus insecticides.

17. ◘ The action of Scopolamine ( Hyoscine ) differs from that of Atropine and Hyoscyamine in that there is No central nervous system stimulation. ◘ Hyoscine HBr is commonly used in as antispasmodic, sedative , and CNS depressant . USES of Scopolamine (Hyoscine)

18. CNS effect of the plant vs major isolated Alkaloid(s)?!!! Belladonna, Datura and Hyoscyamus vs Atropine and Hyoscyamine

19. Isolation of solanaceous alkaloids Atropine, Hyoscyamine and Hyoscine Principle ◘ Separation of hyoscine from both atropine and hyoscyamine depends on the difference in their basicity. Hyoscine is a weaker base . ◘ Separation of atropine from hyoscyamine is based on the difference in the solubility of their oxalates in a mixture of acetone and ether

20. The concentration determined by comparison of the observed optical rotation with the known specific rotation.

21. Chemical tests of Tropane Alkaloids Vitali -Morin’s Test:

22. Hyoscine Hyoscyamine Atropine Red White ppt. Green. Red Red Red color on heating. Green Red Bright purple Red color . Green Red Chemical Tests: Vitali's Test : Gerard Test sol. + HgCl 2 Schder's Test 30 vol. H 2 O 2 + Conc.H 2 SO 4 PDMAB . + alkaloidal residue

23. Dried leaves of Erythroxylum coca known as Bolivian coca or Erythroxylum truxillens known as Peruvian coca Family Erythroxylaceae . Coca alkaloids

24. * Coca alkaloids are classified according to the chemical structures into 3 basic types : 1) Ecgonine derivatives ( 2-carboxy-tropine ). [ base of Cocaine] e.g. Cocaine, Cinnamyl Cocaine and  - and  - Truxillines . 2) Psudotropin derivatives e.g. Tropacocaine and Velerine . 3) Pyrrolidine derivatives e.g. Hygrine

25. ◘ Ecgonine base contain both acidic and alcoholic groups. ◘ The acidic group is esterified, with CH 3 OH ◘ The alcoholic group is esterified with different acids, giving different alkaloids. ◘ Major examples: Cocaine and Cinnamyl -cocaine. Ecgonine derivatives

26. ◘ Cocaine is a methylbenzoyl ecgonine ( The Carboxyl group is esterified with methanol and the hydroxyl group is esterified with benzoic acid ) ◘ Cocaine is a 3ry amine ( basic ) and a diester of ecgonine ( Diester Alakloid ) ◘ Cinnamoylcocaine has a cinnamoyl group instead of the benzoyl group of cocaine

27. Isolation of Cocaine (from Peruvian coca leaves) ◘ Most cocaine manufacture continues to take place in Bolivia, Colombia and Peru. Together these countries report the majority of cocaine. ◘ Digest the leaves with lime or Na 2 CO 3 solution and extracting with petroleum ether. ◘ The alkaloid is then extracted by dil. HCl ◘ The acidic solution is conc., where crystals of cocaine HCl are obtained .

28. By Robinson’s condensation between Succinaldehyde + Methyl amine + Acetone dicarboxylic acid methyl ester as follows: Synthesis of Cocaine

29. Chemical tests:

30.  - and  - Truxillines In these alkaloids the benzoic acid is replaced by  and  - Truxillin acids (Dimers of cinnamic acid).

31. Pyrrolidine derivatives Hygrine and Cuscohygrine

32. Hygrine ◘ It occurs in coca leaves. ◘ It is a non-ester strongly basic liquid alkaloid . ◘ It gives characteristic crystals with gold chloride and platinic chloride .

33. Cuscohygrine ◘ Is the principal non-ester alkaloid in coca leaves ◘ It occurs as an oily alkaloid , containing two tertiary nitrogen atoms . ◘ It is miscible with water. ◘ It gives characteristic hydrobromide and nitrate salts .

34. * Cocaine is a local anaesthetic for topical application. It is rapidly absorbed by mucous membranes and paralyses peripheral ends of sensory nerves. * As a constituent of Brompton’s cocktail (cocaine and heroin in sweetened alcohol). * Control pain in terminal cancer patients . * Cocaine is very toxic narcotic alkaloid, although it has a C.N.S. stimulant action . followed by a hypnotic effect. Uses

35. ◘ Cocaine is quickly absorbed through mucous membranes. ◘ 50 mg of Cocaine leads to euphoria and hallucination. ◘ Larger doses lead to cerebral cramps, hyperirritabilities and paralysis. ◘ Cocaine is an addictive drug.