Tropane alkaloids notes


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Tropane alkaloids notes

  1. 1. TROPANE ALKALOIDS Kratika Daniel (Ph.D) Assistant professor MANDSAUR INSTITUTE OF PHARMACY, Mandsaur KRATIKA8/30/2012 Kratika Daniel (Ph.D) 1 Assistant professor MANDSAUR INSTITUTE OF PHARMACY
  2. 2. TROPANE ALKALOIDS COCAINE ALKALOID ATROPINE ALKALOID Atropine alkaloid is mainly found in member of solanaceae family in different concentration: -  Atropa belladona (0.4 – 1%)  Datura stromonium (0.2%)  Hyosymus niger (0.05%)• Other solanaceous alkaloid are Hyosyamine, Hyoscine (Scopolamine), Apoatropine, Belladonine.8/30/2012 Kratika Daniel (Ph.D) 2
  3. 3. ISOLATION Powdered drug/ juice + moisten drug with aqueous solution of K2CO3 Extract with CHCl3 Evaporate solvent Extract with Dil. H2SO4 Acidic extract made alkaline by K2CO3 Atropine precipitate out Crystallize by use of alcohol8/30/2012 Kratika Daniel (Ph.D) 3
  4. 4. BIOSYNTHESIS COOH NH2 CHCOOCH3 acetate phenylalanine H3C N CHOCOC6H5 NH2 CH2 Ornithine Cocaine COOHSTEP - 1 decarboxylation NH2 NH2 NHCH3 NHCH3 δ- N - methyl ornithine N - methyl putrescine oxidation acetoacetic acid + N CH3X CHO N - methyl - δ − pyrrolinium salt NHCH3 4-(methylamino)butanal N CH3 O + N CH3 O aldol N CH3 O dehydrogenation condensation hygrine tropinone reduction 8/30/2012 NKratika 3 CH Daniel (Ph.D) OH 4 tropine
  5. 5. STEP 2 COOH O OH COOHHO OH NH2 O OH shikmic acid phenyl alaine phenyl pyruvic acid COOH C CH2OH H tropic acid8/30/2012 Kratika Daniel (Ph.D) 5
  6. 6. STEP - 3 COOH C CH2OH + N CH3 OH H tropine tropic acid heat HCl O CH2OH N CH3 O C CH Atropine/ Hyosyamine HC OCO CH N CH3 O 8/30/2012 Kratika Daniel (Ph.D) 6 CH2OH scopolamine
  7. 7. Identification test1.(Vitali – Morin reaction): - Alkaloid/ atropine (1µg) + Drop of H SO 2 4 Evaporate to dryness Indicates Which produce Add 0.3ml of 3% solution of presence of atropine bright purple color KOH in methyl alcohol2. On addition of AgNO3 solution to solution Yellowish of hyoscine hydrobromide white ppt Insoluble – HNO3 Soluble – Dil. NH3 8/30/2012 Kratika Daniel (Ph.D) 7
  8. 8. General Test For Alkaloids Mayer reagents : - (potassium mercuric iodide solution) give white ppt. Dragondroff’s reagent: - (KI + bismuth nitrate) orange red ppt Wagner’ s reagent: - (iodine solution) brown ppt. Hager’s reagent: - (saturated solution of picric acid) crystalline yellow ppt. Freshly prepared solution of tannic acid (5%w/v) buff ppt insoluble in NH3 8/30/2012 Kratika Daniel (Ph.D) 8
  9. 9. TLC• 1% solution of atropine dissolved in 2N acetic acid isspotted over silica gel G plate and eluted in the solventsystem of strong NH3 solution – methanol (! : 5 : 100).• TLC plate is spread with an acidified iodoplatinate solution.•Rf – 0.18.•Solvent system – Acetone – 0.5 sosium chloride solution.•Spraying reagents – Dragondroff’s reagent. 8/30/2012 Kratika Daniel (Ph.D) 9
  10. 10. Chemistry & Properties•Melting point – 115oC to 116oC.•Molecular formula – C17H23NO3•On hydrolysis it gives alcohol, tropine, and tropic acid which indicates that atropine is an ester. C17H23NO 3 + H2O C8H9NO + C19H10O 3 atropine tropine tropic acid•It is optically inactive (±) atropine is racemate form of hyoscyamine.• Solubility – Insoluble in ether. Easily soluble in chloroform, alcohol. Sparingly soluble in water. 8/30/2012 Kratika Daniel (Ph.D) 10
  11. 11. SAR H2C CH CH2 O H3C N HC O C CH H2C CH CH2 CH2OH1. The primary part of attachment to cholinergic sites is through the positively charged nitrogen (cationic head). * In tertiary amines, they are quaternized by protonation at physiological pH which causes lack of CNS activity.2. For hydrophobic bond formation & vander waal interaction on aryl group (phenyl thienyl) & a cycloaliphatic (cyclohexyl) is necessary.3. The presence of free hydroxyl or carbamide is also importat for hydrogen bonding with receptor.4. L – hyoscyamine is more active than d- isomer.5. Difference b/w hydroxyl group & quaternqry nitrogen is b/w 2o to 3o.6. It has similar structure to acetylcholine but contain additional substituent which enhance bindig to receptor. 8/30/2012 Kratika Daniel (Ph.D) 11
  12. 12. 7. It has acetic acid ester of amino alcohol which is therapeutically useful. Minimal structure necessary for pure atagoistic activity is due to H5C6 O CH C O CH2 CH2 N(R)2 R R = hydroxy alkyl, alkyl, cycloalkyl, or heterocyclic R’ = alkyl. 8. The high potency of ester and amides of tropic acid result from their ability to H – bond with suitable group o the receptor, surrounded by hydrophobic area. CH2OH H5C2 CH C N CH2 N 8/30/2012 OKratika Daniel (Ph.D) 12
  13. 13. USES & ACTION 1.It has stimulant action on CNS & depress the nerve ending to the secretor glands. 2.It is useful in ophthalmic products b/c it dilates the pupil of eye (mydrasis). 3.Antispasmodic action – GIT motility is inhibited & gastric secretion is inhibited. 4.CVS – alters heart rate, stimulation of vagus nerve, bradycardia. 5.Inhibition of secretion – Salivary, Lachrymal, Bronchial, & Scrotal gland. Producing an uncomfortably dry mouth & skin. 8/30/2012 Kratika Daniel (Ph.D) 13