Phyto Alkaloid Lecture Notes PDF

VI- Isoquinoline Alkaloids a) Ipecacuanha alkaloids: emetine, psychotrine, cephaline. b) Curare alkaloids: d-tubocurarine and curine. c) Hydrastis alkaloids: hydrastine and berberine d) Opium alkaloids: papaverine and narcotine.  VI- Alkaloids of the Isoquinoline group...

VI- Isoquinoline Alkaloids a) Ipecacuanha alkaloids: emetine, psychotrine, cephaline. b) Curare alkaloids: d-tubocurarine and curine. c) Hydrastis alkaloids: hydrastine and berberine d) Opium alkaloids: papaverine and narcotine.  VI- Alkaloids of the Isoquinoline group a) Ipecacuanha alkaloids Sources: Dried roots and rhizomes of Cephaelis ipecacuanha (Rio or Brazillian Ipecacuanha) and Cephaelis acuminata (Cartagena or Panama Ipecacuanha) (F: Rubiaceae). Examples: emetine, psychotrine and cephaline O O O NH HO N VI- Alkaloids of the Isoquinoline group O O NH O HO N Psychotrine  VI- Alkaloids of the Isoquinoline group O O NH O O 1) Reduction N 2) Methylation Methylation Emetine O O O O NH O NH O HO HO N N Reduction Psychotrine Cephaline  VI- Alkaloids of the Isoquinoline group Emetine: - Levorotatory. - Non-phenolic (does not dissolve in KOH or NaOH). - It contains two basic nitrogen atoms. Cephaline: - Levorotatory. - Phenolic (dissolves in caustic alkalies e.g. KOH or NaOH). - It gives emetine on methylation with dimethyl sulphate [(CH3)2SO4]. Psychotrine: - Phenolic (dissolves in caustic alkalies e.g. KOH or NaOH). - It gives cephaline on reduction. - It gives emetine on reduction and methylation.  VI- Alkaloids of the Isoquinoline group Isolation of Ipecacuanha alkaloids Alcoholic extract 1) dil. HCl (to give HCl salts of alkaloids) 2) NaOH (to liberate free bases and then forms Na salts with phenolic alkaloids) 3) Extract with ether Aqueous solution Ether layer Na salts of Cephaline, Psychotrine Emetine (non-phenolic) (Na salts are ether insoluble) (Ether soluble) 1) dil. HCl (to liberate free bases from their Na salts and form HCl salts) 2) NH4OH (to liberate free bases) 3) Extract with ether Cephaline Psychotrine extract with CHCl3 (Ether soluble) (Ether insoluble)  VI- Alkaloids of the Isoquinoline group Ch. Tests: 1) With Froehd's reagent: a) Emetine: gives dirty green color fades on addition of HCl. b) Cephaline: gives dirty green color changes to greenish blue by HCl. c) Psychotrine: gives Pale green color. 2) With p-nitrodiazobenzene: Phenolic alkaloids ONLY give a dye soluble in NaOH Purple color. 3) Psychotrine + conc. H2SO4 + HNO3 gives cherry red color.  VI- Alkaloids of the Isoquinoline group Uses: a) Emetine and psychotrine are emetic. b) Emetine and Cephaline hydrochlorides are anti-amebic (for Amebiasis) and for treatment of Fasciola. c) Total crude alkaloids are used as expectorant in cough mixtures. d) Ipeca alkaloids are diaphoretic alone or in combination with opium (as Dover’s powder).  VI- Alkaloids of the Isoquinoline group b) Curare alkaloids Sources: Chondrodendron species (F: Menispermaceae). Curare is used as an arrow poison. Examples: curine (minor) and d-tubocurarine (major). O O N + N HO HO O CH2 O CH2 H2C OH O H2C OH O N + N O O d- Tubocurarine Curine  VI- Alkaloids of the Isoquinoline group Isolation of Curare alkaloids Method 1: Aqueous extract NH4OH, filter Filtrate Crystalline residue HgCl2 1) Filter PPt. (insoluble complex) 2) Purify by ether H2S (to decompose the complex) Curine d-tubocurarine Method 2: Extract with CHCl3 Curine is only soluble (because d-tubocurarine is insoluble in CHCl3 but soluble in water).  VI- Alkaloids of the Isoquinoline group Properties of d-tubocurarine: - Quaternary base so it is freely sol. in water but insol. in ether and CHCl3. - Dextrorotatory and phenolic alkaloid. Properties of Curine: - 3ry alkaloid so it is sol. in organic solvents and insol. in water. - It occurs in both d- and l-forms. Ch. tests: - Sat. aq. Soln. + FeCl3 Weak green colour Warm Colour intensifies (due to the phenolic nature of these alkaloids).  VI- Alkaloids of the Isoquinoline group Uses: a) Skeletal muscle relaxant (in surgery to produce muscle relaxation without deep anaesthesia). b) It controls and reduces convulsions of strychnine. c) Treatment of mental diseases. d) Diagnostic aid in Myasthenia gravis.  VI- Alkaloids of the Isoquinoline group c) Hydrastis alkaloids Sources: Hydrastis species (F: Berberidaceae). Examples: Hydrastine and Berberine. Uses: astringents in inflammation of the mucous membranes O O O N H H O N+ O O O O O O Hydrastine Berberine VII- Opium Alkaloids  VII- Opium Alkaloids Sources: Dried latex of full grown but unripe capsules of “Opium poppy” Papaver somniferum (F: Papaveraceae). They are classified into 4 groups acc. To their chemical nature: 1) Benzylisoquinoline: e.g. papverine and narcotine. 2) Phenyl ethyl amine: e.g. narceine 3) Diisoquinoline: e.g. cryptopine and protopine 4) Phenanthrene: e.g. morphine, codeine and thebaine  VII- Opium Alkaloids a) Benzylisoquinoline alkaloids They include the weakly basic alk.: papaverine and narcotine (noscapine) Papaverine: a) Soln. in conc. H2SO4 is colorless (on cold) but turns red when heated to 110°C. O b) Warren′s test: N O - This test distinguishes it from other Opium alkaloids. CH2 - Crystals of KMNO4 are crushed and mixed with papaverine, Marqui′s reagent is added Green color changes to blue O O Uses: Smooth muscle relaxant and antispasmodic.  VII- Opium Alkaloids Narcotine (Noscapine): Δ O a) Alk. Soln. + conc. H2SO4 violet color b) Alk. Soln. + conc. H2SO4 + sugar Δ O N greenish yellow colour changes to intense blue O O O How can we differentiate between Papaverine, O Cryptopine (very toxic) and Narcotine? O By conc. H2SO4: - Cryptopine gives red colour on cold. - Papaverine gives no colour on cold and turns red after heating. - Narcotine gives violet colour after heating.  VII- Opium Alkaloids b) Phenyl ethylamine alkaloids Narceine: O Alk. Soln. + dil. H2SO4 Δ violet color O N Δ cherry red cool bluish violet streaks O O COOH - It is a weak base (WHY?). O O - It is a 3ry amine, with carboxylic, carbonyl and methylenedioxy groups.  VII- Opium Alkaloids c) Phenanthrene alkaloids Examples: Morphine, codeine and thebaine. As the poppy fruits ripen, the content of morphine decreases. They have strong basic characters and can be titrated by a standard mineral acid and form stable salts (c.f. the weak basic isoquinoline opium alkaloids). R H3CO O O N CH3 N CH3 HO H3CO Morphine: R=OH Thebaine Codeine: R=OCH3  VII- Opium Alkaloids Morphine: ❑Unlike most alkaloidal free bases, the free base of morphine is sparingly soluble in CHCl3 and insoluble in ether or benzene. ❑It contains a phenolic OH group and another secondary alcohol OH group. ❑Because of its phenolic nature, it dissolves in caustic alkalies. HO O N CH3 Morphine HO  VII- Opium Alkaloids Morphine: ❑On methylating the phenolic OH group, it gives codeine. ❑On oxidation, the alc. OH is converted to a ketonic group to give codeinone. ❑Acetylation of morphine gives diacetyl morphine (Heroin) which is a very potent narcotic. ❑On heating with conc. HCl, morphine loses water to give apomorphine. HO HO HO O N CH3 CH3 N HO Morphine Apomorphine  VII- Opium Alkaloids ❑Ch. Tests: 1) Brouadrel-Boutmy test: - Soln. of Alk. Salt + pot. ferricyanide + FeCl3 gives deep blue colour. - This test depends on the reducing action of morphine (phenolic alk.) on pot. ferricyanide which is converted to pot. ferrocyanide and this gives prussian blue colour with FeCl3. Codeine does not give this test (WHY?). 2) Schneider-Weppen test: - Morphine + powdered cane sugar + conc. H2SO4 gives purple red colour.  VII- Opium Alkaloids 3) Nitrous acid test: - Soln. of Alk. Salt in HCl + NaNO2 + KOH gives rose red colour. - This red colour is proportional to the concentration and can be used in colorimetric estimation of morphine. 4): Morphine + conc. HNO3 orange red colour Δ yellow colour SnCl2 The colour is destroyed (it fails to give a violet colour c.f. brucine).  VII- Opium Alkaloids Codeine: ❑It is methyl morphine in which a CH3 gp. replaces the H of the phenolic OH gp. Thus, codeine is non-phenolic and less narcotic than morphine. ❑It is soluble in water, ether, CHCl3 and benzene (c.f. morphine). ❑Codeine + conc. H2SO4 + FeCl3 Δ bluish violet color conc. HNO3 red color ❑Codeine + HNO3 yellow color H3CO ❑Codeine + FeCl3 -ve O N CH3 HO  VII- Opium Alkaloids Thebaine: ❑It has neither phenolic nor alcoholic groups ❑Thebaine + conc. H2SO4 Red color changes to orange yellow (compare with isoquinoline alkaloids of opium). H3CO O N CH3 H3CO Thebaine  Item Morphine Codeine Structure Contain 2 OH gps. (one phenolic Methyl morphine (contain and the other alc.) one alc. OH group) Nature phenolic non-phenolic Solubility in CHCl3, insoluble soluble ether, benzene With caustic Dissolve and form salts Does not dissolve alkalies (morphinate) Brouadrel-Boutmy Prussian blue color -ve test With HNO3 Orange red color Yellow color With FeCl3 Blue color -ve (non-phenolic) (test for phenols)  VII- Opium Alkaloids ❑Opium alkaloids are usually found as salts together with Meconic acid. ❑The positive detection of this acid is a proof for presence of opium or any of its preparations. ❑Test for Meconic acid: - Aq. Soln. + FeCl3 deep red colour - The colour is not destroyed by boiling or by addition of HCl. HOOC O COOH OH O Meconic acid  VII- Opium Alkaloids Pharmacological actions and uses of Opium alkaloids: 1) Morphine: a) Narcotic analgesic alkaloid for post-operative pain and cancer patients. b)It exerts a CNS depressant action (hypnotic and narcotic). Disadvantages: - Causes respiratory depression. - Develops rapid tolerance to its action. - Causes addiction. 2) Codeine: a) Resembles morphine in its action, but it is much weaker and less toxic. b) There is less tendency to tolerance and addiction than morphine. c) Used as analgesic, antitussive, and as a sedative to calm dry coughs.  VII- Opium Alkaloids 3) Benzyl isoquinoline alkaloids: a) They have no narcotic properties and exert no analgesic action. b) Narcotine: - Has NO narcotic properties. - Relaxes smooth muscles. - Used as anti-tussive. c) Papaverine: - Relaxes smooth muscles (acting directly on the muscle) (i.e. antispasmodic) - Prolongs the refractory period of the heart. - Was used in bronchial asthma and myocardial infarction, but its effect has been questioned. 4) Phenyl ethyl amine alkaloids:(Narceine): not used as a medicinal agent  Opium alkaloids CaCl2 soln., extract with warm H 2O Filtrate Residue (ppt) HCl alkaloidal salts Calcium meconate, Calcium lactate,… NaOH Filtrate Residue Morphine, codeine, narceine Papaverine, narcotine, thebaine CHCl3 Dissolve in alcohol, acidify with acetic acid CHCl3 Aqueous Codeine NH4OH Filtrate Residue Thebaine Oxalic acid Filtrate Residue ppt filtrate Narceine Morphine Papaverine Narcotine  VII- Opium Alkaloids NOTES: 1) Addition of CaCl2 solution: a) To precipitate the acids and resin present in opium. b) To liberate HCl acid which converts the alkaloids to soluble salts. 2) NaOH dissolves morphine (phenolic) forming Na morphinate. 3) Codeine is soluble in NH4OH and NaOH but insoluble in excess of alkali. 4) Narceine (acidic) dissolves in excess of alkali forming Na salt.