Tropane alkaloids notes
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  • 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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