More Related Content

More from Mostafa Mahmoud Hegazy(20)



  1. 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).
  4. Tropane Alkaloids Tropane is a bicyclic, 7-membered compound formed by the condensation of Pyrrolidine and Piperidine with one nitrogen atom. Piperidine N H Pyrrolidine (C4N) N H Tropane N CH3
  5. H N L-Ornithine NH2 NH2 COOH N H
  6. H N N H L-Ornithine NH2 NH2 COOH
  7. N H H N L-Ornithine NH2 NH2 COOH
  8. Tropane N CH3 L-Ornithine NH2 NH2 COOH
  9. L-Ornithine NH2 NH2 COOH Tropane N N H3C 1 2 3 4 5 6 7 CH3 = ◘ Tropane nucleus is a seven carbon bicyclic ring. nitrogen bridge is between Carbons 1 and 5
  10. ◘ 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.
  11. Alcoholic bases in Tropane Alkaloids
  12. 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
  13. Esterifying acids in Tropane Alkaloids
  14. 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.
  15. 1) Atropa belladonna (Belladonna Leaves). 2) Datura stramonium (Thornapple). 3) Hyoscyamus niger (European henbane) 4) Hyoscyamus muticus (Egyptian henbane) SOLANACEOUS ALKALOIDS
  16. Solanaceous Alkaloids N O Me O H CH2OH (-)-Hyoscyamine N O O CH2OH Me Atropine  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).
  17. Number of atropine chiral center(s)? N O O CH2OH Me Atropine  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).
  18. 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
  19. 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
  20. 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.
  21. ◘ 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)
  22. CNS effect of the plant vs major isolated Alkaloid(s)?!!! Belladonna, Datura and Hyoscyamus vs Atropine and Hyoscyamine
  23. 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
  24. The concentration determined by comparison of the observed optical rotation with the known specific rotation.
  25. Chemical tests of Tropane Alkaloids Vitali-Morin’s Test: * 1 mg of alkaloid + Fuming HNO3 * Evaporated to dryness on a water bath Yellow residue * Cooled * Add few drops of 3% alc. KOH solution Bright purple or Violet color
  26. 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. + HgCl2 Schder's Test 30 vol. H2O2 + Conc.H2SO4 PDMAB. + alkaloidal residue
  27. By Robinson's condensation between succinaldehyde, Synthesis of atropine H2C H2C C C O O H H N CH3 H H H H C C C COOH H COOH H N H3C COOH HOOC O + + N H3C O N H3C OH O dl-tropic acid Atropine + -2 H2O NaBH4 Succinaldehyde Methyl amine Acetone dicarboxylic acid Tropinone dicarboxylic acid Tropinone Tropine Reduction Esterification - 2CO2 methyl amine and acetone dicarboxylic acid as follows:
  28. Dried leaves of Erythroxylum coca known as Bolivian coca or Erythroxylum truxillens known as Peruvian coca Family Erythroxylaceae. Coca alkaloids
  29. * 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 a- and b-Truxillines. 2) Psudotropin derivatives e.g. Tropacocaine and Velerine. 3) Pyrrolidine derivatives e.g. Hygrine
  30. ◘ Ecgonine base contain both acidic and alcoholic groups. ◘ The acidic group is esterified, with CH3OH ◘ The alcoholic group is esterified with different acids, giving different alkaloids. ◘ Major examples: Cocaine and Cinnamyl-cocaine. Ecgonine derivatives
  31. N H3C C O OCH3 O C O N H3C C O OCH3 O Cinnamoylcocaine O Cocaine ◘ 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
  32. 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 Na2CO3 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.
  33. By Robinson’s condensation between Succinaldehyde + Methyl amine + Acetone dicarboxylic acid methyl ester as follows: Synthesis of Cocaine
  34. H2C H2C C C O O H H N CH3 H H H H C C C COOCH3 H COOH H N H3C COOCH3 HOOC O N H3C O N H3C OH O - 2H2O NaBH4 COOCH3 COOCH3 N H3C O COOCH3 C O + + Benzoic anhydride + Succinaldehyde Methyl amine Acetone dicarboxylic acid mono methylester Reduction Esterification Cocaine -CO2
  35. Chemical tests:
  36. a- and b-Truxillines In these alkaloids the benzoic acid is replaced by a and b -Truxillin acids (Dimers of cinnamic acid). C6H5 H COOH H H C6H5 H COOH C6H5 H C6H5 COOH H H HOOC H a-Truxillic acid bTruxillic acid
  37. N H3C 1 2 3 4 5 6 7 8 O COOCH3 O O O N COOCH3 CH3 N H3C 1 2 3 4 5 6 7 8 O COOCH3 O N H3C 1 2 3 4 5 6 7 8 O H3COOC a-truxilline b-truxilline
  38. Pyrrolidine derivatives Hygrine and Cuscohygrine N O Me (+)-Hygrine N O Me N Me Cuscohygrine
  39. 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.
  40. 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.
  41. * 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
  42. ◘ 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.