PHG 322 Pharmacogonsy II lecture 2 Presented by Assistant Prof. Dr. Ebtesam Alsheddi

1. PHG 322Pharmacogonsy IIlecture 2Presented byAssistant Prof. Dr. EbtesamAlsheddi بسم الله الرحمن الرحيم

2. conc HCl or HI sublimeswithout decomposition + CH3Cl or CH3I apomorphine Stability: • Generally alkaloids are decomposed by heat except: caffeine • Effect of Acids: • hot dil. acids or conc. mineral acids may cause: Dehydration O-demethylation Next page ! codeine e.g. apoalkaloids e.g. morphine morphine

3. e.g. atropine e.g. solanine Stability: (cont.) • Effect of Acids: (cont.) • hot dil. acids or conc. mineral acids may cause: Hydrolysis of -glucoalkaloids: - ester alkaloids:

4. Na salt Stability: (cont.) • Effect of Alkalies: Effect of weak alkalies Effect of strong alkalies Effect of hot dil. alkalies form salts with alkaloids containing carboxylic group e.g Narceine + NaHCO3 liberate most alkaloids from their salts

5. salt (phenates) e.g. atropine corresponding acid b) Effect of strong alkalies: phenolic alkaloid + aq. NaOH or KOH c) Effect of hot dilute alkalies: hydrolysis of ester alkaloids cleavage of lactone ring e.g. pilocarpine Pilocarpic acid

6. Tests for identification: include two types of reactions: Precipitation reactions Colour reactions 1) Precipitation reactions: precipitating reagent aqueous soln. of alkaloidal salts + (contains heavy metals e.g. Hg, Cd, Bi, …) Coloured ppts (amorphous or crystalline) N.B. • certain alkaloids do not react e.g. caffeine • false positive resultsare possible most reagents precipitate: proteins, tannins, …

7. Classification of Alkaloidal precipitating agents: 1- Reagents that form double salts: a- Mayer’s Reagent: Potassium Mercuric Iodide. b- Dragendorff’s Reagents: Potassium Iodobismethate. c- Gold Chloride. 2- Reagents Containing Halogens: a- Wagner’s Reagent: Iodine/ Potassium Iodide. 3-Organic Acids: a- Hager’s Reagent: Picric Acid b- Tannic Acid. 4- Oxygenated High Molecular Weight Acids: a- Phosphomolybdic acid b- Phosphotungestic acid c- Silicotungestic Acid

8. colour reagent + characteristic colour solid (free base) (contain conc H2SO4 + an oxidizing agent) • Colour Reagents: 1- Froehd’s Reagent: Phosphomolybdic acid 2- Marqui’s Reagent: Formaldehyde/ Conc. H2SO4 3- Mandalin’s Reagent: Sulphovanidic acid 4- Erdmann’s Reagent: Conc. HNO3/Conc. H2SO4 5- Mecke's Reagent:Selenious acid / conc. H2SO4 6- Shaer's Reagent: Hydrogen peroxide / conc. H2SO4 7- Rosenthaler's Reagent: Potassium arsenate / conc. H2SO4 8- Conc. HNO3 These tests are sensitive to micro amounts used for colourimetric determination (quantitative)

9. violet colour blue colour - specific for one alkaloid or a group of related alkaloid: 1)Vitalis test for solanaceous alkaloids: + conc HNO3 & alc. KOH 2) Van-Urks test for ergot alkaloids: + PDAB in conc H2SO4

10. N.B. • + vewith: -most alkaloids CNS stimulant Caffeine & strychnine Analgesic & narcotics Morphine Anti-tussive Codeine Mydriatic Atropine Anticancer Vincristine, vinblastine, taxol Pharmacological activity: wide range of pharmacological activities 10

11. 14 major groups • Chemical classification: Non-heterocyclic Heterocyclic = Atypical alkaloids (Protoalkaloids) = typical alkaloids according to ring structure

12. Alkaloids of the Pyridine nucleus: classifiedaccording to building nucleus into: Pyridine nucleus only Pyridine nucleus +another nitrogenous ring Tetrahydro-pyridine nucleus Piperidine nucleus Pyridone nucleus 12

13. non-volatile liquid nicoteine (-)-nicotine (major) Volatile liquids 1) Pyridine alkaloids containing another nitrogenous ring: e.g. Tobacco alkaloids nor-nicotine

14. aq. soln + PDAB nicotine + picric acid rose redcolour gradually violet colour less basic air or light form salts with acids Nicotine Properties: • Colourless or pale yellow oily liquid brown Colour tests 2 basic N atoms Tests: Crystals

15. due to high toxicity respiratory stimulant respiratory depressant Pharmacological actions & uses: • Little use in medicine • In small doses • In larger doses • Increases incidence of abortion • Main use: Insecticide & anthelmintic in veterinary medicine

16. + acid 2) Piperidine alkaloids: • e.g. alkaloids of: a) Black pepper b) Conium d) Pomogranate c) Lobelia a) Pepper alkaloids: • Occurrence: fruitsofPiperspecies e.g.P. nigrum • Major alkaloid: piperine No salt • It is very weak basic + H2SO4 • Colour tests Red colour

17. + alc KOH Piperic acid Piperidine + blue crystals • soluble in: CHCl3 & EtOH • insoluble in: H2O • Piperine Crystal tests alc. soln. + Wagner`s reag.

18. loss of taste budsin tongue Uses: • Mainly as condiment • Little use in medicine • Used in rubefacient preparations Chronic toxicity: • Prologed use at high doses

19. c- Lobelia alkaloids • Occurrence: the dried aerial parts of Lobelia inflata.(indiantobacoo) • Major alkaloid: Lobeline crystalline)

20. Uses: -Asthma -Chronic bronchitis -Anti-smoking preparations -Injection of lobeline hydrochloride is used in the resuscitation of newborn infants. • Caution: Toxic doses the herb has a paralytic effect

21. d- Pomegranate alkaloid • Occurrence: the fruit rind, root bark and stem bark of Punicagranata • Major alkaloid: pelltierine (liquid) pelletierinetannate (mixture, solid) Alkali decompose it to give free alkaloids Pomegranates have astringent properties because of the alkaloids (pelletierinetannate) present in the bark of the stems and roots and have been used for many years as an anthelmintic: removing tapeworms

22. > 50% II. Alkaloids of the Quinoline group • Most important → Cinchona alkaloids Cinchona alkaloids • Present in the barkCinchona species - Cinchona ledgeriana & C. calisaya (yellow Cinchona) - C. succirubra (red Cinchona) F. Rubiaceae • e.g. of alkaloids: two groups of stereoisomers: Quinine (l)& Quinidine (d) Cinchonidine (l)& Cinchonine (d)

23. Quinine (Cinchonidine epimer at C-9) Quinidine (Cinchonine epimer at C-9) Structure: H Cinchonine&cinchonidine OCH3 Quinine & quinidine (few drops till yellow colour appears) Quinine: • Intensely bitter solid

24. Emerald green colour Quinine (l) gives Quinidine (d) among other products when warmed with KOH in amyl alcohol Cinchonine & Cinchonidine are less soluble in H2O than quinine & quinidine Test: 1) Fluorescence test: + dil H2SO4 Fluorescence + ve forquinine&quinidine 2) Thalleoquine test: aq. soln of alkaloidal salt + Br2/H2O + NH4OH

25. used as used as • Quinine as Quinine sulphate or other salts has febrifuge effect Uses: anti-malarial (contra indicated in pregnancy as it causes abortion) cardiac depressant (anti-arrythmic) • Quinidine • Cinchonine and Cinchonidine are used as anti-rheumatic

26. Vinyl group loss of activity decreases activity Structure activity relationship: • For antimalarial activity (Quinine): - Removal of vinyl group - Replacement of CHOH by: - CHCl, CH2, CO

27. III. Alkaloids of the Isoquinoline group Ipecacuanha Opium (Papaverine type)

28. Isoquinoline Alkaloids1- Ipecacuanha Alkaloids • Occurrence: Ipecac is the dried roots and rhizomes of Cephalisipecacuanha (Brazilian ipecacuanha) or Cephalisacuminata(Cartagena or Panama ipecacuanha) Fam. Rubiaceae. It contains several alkaloids (2 –2.5 %), mainly emetine (50- 70 % of total alkaloids), with cephaline and psychotrine.

29. Emetine: • It is non phenolic and levorotatory. It contains 2 basic nitrogens. • Cephaline: It is phenolic and levorotatory. It gives emetine on methylation with (CH3)2 SO4. • Psychotrine: Occurs as yellow prisms. It is phenolic and gives cephalineon reduction. It gives emetine on reduction followed by methylation.

30. Tests for identification of Ipeca alkaloids: • Alkaloidal solution in HCl + Ca hypochlorite orange color. • Emetine and cephaline + Froehd'sreagent:dirty green color (the color with emetine fades by addition of HCl). • Psychotrine + Froehd'sreagent:pale greencolor. • Cephalineandpsychotrine + p-nitrodiazobenzene dye soluble in NaOHpurple color. • Psychotrine + conc. H2SO4 +HNO3cherry red color. • Emetine + Liebermann's reagent black color.

31. Uses: • Emetine and cephaeline have antitumourandantiviralactivity, but are too toxic for therapeutic use. • Emetine and psychotrineare mainly used as emetic drugs. • The crude drug is used as expectorant (due to its saponin content) . • Emetine HClhas an antiamoebic effect, and are used for the treatment of amoebic dysentry and Fasciola. • Ipeca alkaloids are diaphoretic, alone or in combination with opium (e.g. Dover'spowder).