PHYTOCONSTITUENTS

1. PHYTOCONSTITUENTS Presented by BAHADUR SINGH HOD Department of Pharm. Sciences Govt. Polytechnic college for Girls Patiala

2. PHYTOCONSTITUENTS: Crude drugs are subjected to a suitable method of extraction for the isolation of Phyto pharmaceuticals/ Phyto constituents known as Active Constituents of the Drugs. These are Biosynthesis: Conversion of Simple chemical substances into complex substances with the help of Enzymes. Main group of Phytoconstituents of therapeutic importance are: Alkaloids, Glycosides, Terpenoids, Steroids, carbohydrates, Flavonoids fixed oils etc.

3. Alkaloids Definition: the term “alkaloid” (alkali-like) is commonly used to designate basic heterocyclic nitrogenous compounds of plant origin that are physiologically active.

4. Alkaloids are a group of naturally occurring chemical compounds that contain mostly basicnitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids. In addition to carbon, hydrogen and nitrogen, alkaloids may also contain oxygen, sulfur and more rarely other elements such as  chlorine,  bromine, and phosphorus

5. The name "alkaloids" (German: Alkaloide) was introduced in 1819 by the German chemist Carl F.W. Meissner, and is derived from late Latin root Latin: alkali (which, in turn, comes from the Arabic al-qalwī – "ashes of plants") and the suffix Greek: -οειδής – "like" However, the term came into wide use only after the publication of a review article by O. Jacobsen in the chemical dictionary of Albert Ladenburg in the 1880s.

6. HistoryFriedrich Sertürner, the German chemist who first isolated morphine from opium.Studies of alkaloids began in the 19th century. In 1804, the German chemist Friedrich Sertürner isolated from opium a "soporific principle" (Latin: principium somniferum), which he called "morphium" in honor of Morpheus, the Greek god of dreams; in German and some other Central-European languages, this is still the name of the drug. The term "morphine", used in English and French, was given by the French physicist Joseph Louis

7. A significant contribution to the chemistry of alkaloids in the early years of its development was made by the French researchers Pierre Joseph Pelletier and Joseph BienaiméCaventou, who discovered quinine (1820) and strychnine (1818). Several other alkaloids were discovered around that time, including xanthine(1817), atropine (1819), caffeine (1820), coniine (1827), nicotine (1828), colchicine (1833), sparteine (1851), and cocaine (1860The first complete synthesis of an alkaloid was achieved in 1886 by the German chemist Albert Ladenburg

8. Alkaloid Description Contains nitrogen - usually derived from an amino acid. • Bitter tasting, generally white solids (exception - nicotine is a brown liquid). • They give a precipitate with heavy metal iodides. • Caffeine, a purine derivative, does not precipitate like most alkaloids. • Alkaloids are basic - they form water soluble salts. Most alkaloids are well-defined crystalline substances which unite with acids to form salts. In plants, they may exist • in the free state, • as salts or • as N-oxides. • Occur in a limited number of plants. Nucleic acid exists in all plants, whereas, morphine exists in only one plant species.

9. Deviation from Definition:Basicity: Some alkaloids are not basic e.g. Colchicine, Piperine, Quaternary alkaloids.Nitrogen: The nitrogen in some alkaloids is not in a heterocyclic ring e.g. Ephedrine, Colchicine, Mescaline.Plant Origin: Some alkaloids are derived from Bacteria, Fungi, Insects, Frogs, Animals.

10. Classification:True (Typical) alkaloids that are derived from amino acids and have nitrogen in a heterocyclic ring. e.g AtropineProto alkaloids that are derived from amino acids and do not have nitrogen in a heterocyclic ring. e.g EphedrinePseudo alkaloids that are not derived from amino acids but have nitrogen in a heterocyclic ring. e.g CaffeineFalse alkaloids are non alkaloids give false positive reaction with alkaloidal reagents.

11. Common amino acid precursors: • Phenylalanine • Tyrosine • Tryptophan • Histidine • Anthranilic acid • Lysine • Ornithine • Important general reactions involved: • Decarboxylation The process of removing a carboxyl group from a chemical compound • Transamination The process of transposing an amino group within a chemical compound

12. Distribution and occurrence:Rare in lower plants. Dicots are more rich in alkaloids than Monocots. Families rich in Alkaloids: Apocynaceae, Rubiaceae, Solanaceae and Papaveracea. Families free from Alkaloids: Rosaceae, Labiatae

13. Distribution in Plant:All Parts e.g. Datura.Barks e.g. CinchonaSeeds e.g. NuxvomicaRoots e.g. AconiteFruits e.g. Black pepperLeaves e.g. TobaccoLatex e.g. Opium

14. Forms of Alkaloids: • Free bases • Salts with Organic acids e.g. Oxalic, acetic acids • Salts with inorganic acids e.g. HCl, H2SO4. • Salts with special acids: • e.g. Meconic acid in Opium Quinic acid in Cinchona • Glycosidal form e.g. Solanine in Solanum.

15. Function in Plants • They may act as protective against insects and herbivores due to their bitterness and toxicity. • They are, in certain cases, the final products of detoxification (waste products). • Source of nitrogen in case of nitrogen deficiency. • They, sometimes, act as growth regulators in certain metabolic systems. • They may be utilized as a source of energy in case of deficiency in carbon dioxide assimilation.

16. Nomenclature: Trivial names should end by "ine". These names may refer to: • The genus of the plant, such as Atropine from Atropabelladona. • The plant species, such as Cocaine from Erythroxylon coca. • The common name of the drug, such as Ergotamine from ergot. • The name of the discoverer, such as Pelletierine that was discovered by Pelletier. • The physiological action, such as Emetine that acts as emetic, Morphine acts as narcotic. • A prominent physical character, such as Hygrine that is hygroscopic.

17. Prefixes and suffixes: Prefixes: • "Nor-" designates N-demethylation or N-demethoxylation, e.g. norpseudoephedrine and nornicotine. • "Apo-" designates dehydration e.g. apomorphine. • "Iso-, pseudo-, neo-, and epi-" indicate different types of isomers. Suffixes: • "-dine" designates isomerism as quinidine and cinchonidine. • "-ine" indicates, in case of ergot alkaloids, a lower pharmacological activity e.g. ergotaminine is less potent than ergotamine.

18. Physical Properties: I- Condition: • Most alkaloids are crystalline solids. • Few alkaloids are amorphous solids e.g. emetine. • Some are liquids that are either: Volatile e.g. nicotine and coniine, or Non-volatile e.g. pilocarpine and hyoscine. II- Color: The majority of alkaloids are colorless but some are colored e.g.: • Colchicine and berberine are yellow. • Canadine is orange. • The salts of sanguinarine are copper-red.

19. Physical Properties: III- Solubility: • Both alkaloidal bases and their salts are soluble in alcohol. • Generally, the bases are soluble in organic solvents and insoluble in water Exceptions: • Bases soluble in water: caffeine, ephedrine, codeine, colchicine, pilocarpine and quaternary ammonium bases. • Bases insoluble or sparingly soluble in certain organic solvents: morphine in ether, theobromine and theophylline in benzene. • Salts are usually soluble in water and, insoluble or sparingly soluble in organic solvents. Exceptions: • Salts insoluble in water: quinine monosulphate. • Salts soluble in organic solvents: lobeline and apoatropine hydrochlorides are soluble in chloroform.

20. IV- Isomerization: • Optically active isomers may show different physiological activities. • l-ephedrine is 3.5 times more active than d-ephedrine. • l-ergotamine is 3-4 times more active than d-ergotamine. • d- Tubocurarine is more active than the corresponding l- form. • Quinine (l-form) is antimalarial and its d- isomer quinidine is antiarrythmic. • The racemic (optically inactive) dl-atropine is physiologically active.

21. Chemical Properties: I- Nitrogen: • Primary amines R-NH2 e.g. Norephedrine • Secondary amines R2-NH e.g. Ephedrine • Tertiary amines R3-N e.g. Atropine • Quaternary ammonium salts R4-N e.gd-Tubocurarine II- Basicity: • R2-NH > R-NH2 > R3-N • Saturated hexacyclic amines is more basic than aromatic amines.

22. According to basicity Alkaloids are classified into: • Weak bases e.g. Caffeine • Strong bases e.g. Atropine • Amphoteric * Phenolic Alkaloids e.g. Morphine • *Alkaloids with Carboxylic groups e.g. Narceine • Neutral alkaloids e.g. Colchicine

23. III- Oxygen: • Most alkaloids contain Oxygen and are solid in nature e.g. Atropine. • Some alkaloids are free from Oxygen and are mostly liquids e.g. Nicotine, Coniine.

24. IV- Stability: • Effect of heat: Alkaloids are decomposed by heat, except Strychnine and caffeine (sublimable). • Reaction with acids: 1- Salt formation. 2- Dil acids hydrolyze Ester Alkaloids e.g. Atropine

25. 3- Conc. acids may cause: • Dehydration: Atropine → Apoatropine Morphine → Apomorphine • Demethoxylation: e.g. Codeine

26. Effect of Alkalies:1- Dil alkalis liberate most alkaloids from their salts e.g. NH3. 2- They may cause isomerization (racemization) of alkaloid as the conversion of hyoscyamine to atropine.3- They also can form salts with alkaloids containing a carboxylic group e.g. narceine.4- Strong alkalis: such as aqueous NaOH and KOH form salts with phenolic alkaloids.5- Strong alkalis cause hydrolysis of Ester alkaloids (e.g. atropine, cocaine and physostigmine) and Amide alkaloids ( colchicines).6- Strong alkalis cause opening of lactone ring

27. Effect of light and Oxygen:Some alkaloids are unstable when exposed to light and Oxygen:

28. Qualitative test for Alkaloids: • Precipitation Reagents: They are used to: 1- Indicate the absence or presence of Alkaloids 2- Test for complete of extraction Disadvantages: Some non alkaloids interfere such as Proteins, lactones, coumarins

29. Classification of Alkaloids • Biogenetic. Based on the biogenetic pathway that form the alkaloids. • Botanical Source. According to the plant source of alkaloids. • Type of Amines. Primary, Secondary, Tertiary alkaloids. • Basic Chemical Skeleton

31. Piperidine/Pyridine alkaloids

32. Also referred to as Pyrrolizidine alkaloids Include Lobeline (Lobelia herb) – respiratory stimulant  Used in asthma preparations. Nicotine (Nicotianatabacum and other Nicotinaspp) – toxic  used as an insecticide Lobeline Pyridine Alkaloids

33. Definition: Lobelia herb consists of the dried aerial parts of Lobelia inflata. Common Names: Lobelia, Indian Tobacco) History: Traditionally used by the Native Americans for asthma. Lobelia inflata- Capmanulaceae

34. Contains Pyrrolizidine Alkaloids Most important Lobeline Also Lobelidine Lobelanine Isolobelanine Lobelia inflata – Constituents

35. IMIDAZOLE ALKALOIDS • contain imidazole (glyoxaline) rings PILOCARPINE PILOCARPUS • jaborandi • Consists of leaflets of: • Pilocarpus jaborandi Holmes • PilocarpusmicrophyllusStapf • PilocarpuspinatifoliusLamaire • Indigenous to Brazil

36. Uses: Ophthalmic drugs for treatment of galucoma Applied topically Dosage: 0.05-0.1mL of a 0.25 to 10% solution of Pilocarpinehyrdochloride OR 0.05-0.1mL of a 0.5 to 6% solution of Pilocarpine nitrate Applied to the conjunctiva, 1-6x a day Patients should be advised to wash hands immediately after application.

37. Pilocar® Isopto-carpine®

38. Tropane alkaloids Many of these psychoactive alkaloids

39. Tropane Alkaloids Derived from tropine and consist of mandelic, tropic or benzoic acid esters of tropine. Are very closely related to each other All have pronounced physiological actions. Natural alkaloids include Hyoscyamine Hyoscine Atropine Cocaine The above mentioned alkaloids occur within the Solanaceae family (except cocaine – from Erythroxylaceae family)

40. Atropine Hyoscine

41. Definition: Stramonium Leaf consists of the dried leaves or dried leaves and flowering tops of Daturastramonium. The drug should contain at least 0.25% alkaloids calculated as hyoscyamine. Common names: Stramonium leaf, Thornapple, Jimson or Jamestown weed Daturastramonium - Solanaceae

42. Hyoscyamusalbus (petiolate stem-leaves and pale yellow, non-veined petals – bottom left). Hyosycamusmuticus (top right) Hyoscyamuspusillus Hyoscyamusaureus Hyoscyamusreticulatus (Indian henbane – bottom right) Hyoscyamus niger – Allied Drugs

43. Definition: Belladonna herb consists of the dried leaves and flowering tops of Atropa belladonna, containing at least 0.3% alkaloids (hyoscyamine). Should not contain >3% stem >5mm in diameter. USP also allows A. acuminata in the Belladonna Leaf monograph. Atropa belladonna - Solanaceae

44. Quinoline alkaloids

45. Consist of alkaloids and alkaloid salts obtained from the bark of certain Cinchona species (Quinine, Quinidine, Cinchonine, Cinchonidine). The amount of alkaloids present depend on the species, environment of the tree, age, and method of bark collection. Quinine: Anti-malarial Synthetic alkaloids are now used as substitutes for quinine for malaria. Quinoline Alkaloids

46. Definition: Cinchona bark consists of the various species races and hybrids of Cinchona, large trees indigenous to Colombia Equador, Peru & Bolivia INCLUDES C. Succirubra, C. calisaya, C. ledgeriana, C. officinalis Cinchona Bark - Rubiaceae

47. Bitter tonics Stomachics Used as gargles (tannins in bark – astringent) Malaria Prophylaxis of cardiac arrhythmias Treatment of atrial fibrillation Cinchona Bark - Uses

48. Isoquinoline alkaloids

49. Definition: Opium (Raw Opium) is the latex obtained by incision from the unripe capsules of Papaversomniferum, from the Papaveraceae Family. It is dried partially by spontaneous evaporation and partly by artificial heat. Commercially known as Indian opium. BP monograph: opium is intended only as a starting point for the manufacture of galenicals, and should not be dispensed as such. Opium Alkaloids – Opium

50. 30 Alkaloids 6 main ones Morphine Codeine Thebaine Noscapine Narceine papaverine Papaver somniferum - Constituents