alka

• Alkaloids


  Basic organic heterocyclic nitrogenous compounds usually physiologically active
• Alkaloids


  • Hard to characterize, not a homogenous group
  • Free alkaloids are soluble in ether, chloroform
  • Some alkaloids are not basic e.g. Colchicine, Piperine, and Quaternary alkaloids
  • The nitrogen in some alkaloids is not in a heterocyclic ring e.g Ephedrine, Colchicine, Mescaline
  • Some alkaloids are derived from bacteria, fungi, insects, frogs and animals
• New definition of alkaloids

  Cyclic organic compounds containing nitrogen in a negative state of oxidation with limited distribution among living organisms
• Alkaloids


  • Mostly are physiologically active, some are poisonous
  • Pure alkaloids unite with acid to form substituted ammonium salts, alkaloids are freed from their salt by addition of alkali
  • Contain nitrogen, nitrogen may exist as primary, secondary, tertiary and quaternary amine
  • Usually possess a bitter taste
  • Mostly are crystalline solids, few are amorphous, liquids for those that lacks oxygen
  • Soluble in organic solvent, insoluble in water
  • The majority of alkaloids are colorless but some are colored
  • Decomposes with heat except caffeine
  • Form double bond salts with compound of mercury, gold platinum, and other heavy metals
• Reagents that form double salts with alkaloids


  • Mayer's Reagent - Mercuric Potassium Iodide
  • Dragendorff's Reagents - Potassium Bismuth Iodide
  • Gold Chloride
  • Marme's Reagent - Potassium Cadmium Iodide
• Reagents Containing Halogens


  • Wagner's Reagent - Iodine in Potassium Iodide
• Organic Acid Reagents


  • Hager's Reagent - Picric Acid
  • Tannic Acid
• Oxygenated High Molecular Weight Acid Reagents


  • Sonnenschein's Reagent - Phosphomolybdic acid
  • Scheibler's Reagent - Phosphotungestic acid
  • Silicotungestic Acid
• Other Alkaloid Reagents


  • Froehd's Reagent: Phosphomolybdic acid
  • Marqui's Reagent: Formaldehyde/ Conc. H2SO4
  • Mandalin's Reagent: Sulphovanidic acid
  • Erdmann's Reagent: Conc. HNO3/Conc. H2SO4
  • Mecke's Reagent: Selenious acid / conc. H2SO4
  • Shaer's Reagent: Hydrogen peroxide / conc. H2SO4
  • Rosenthaler's Reagent: Potassium arsenate / conc. H2SO4
  • Conc. HNO3
• Types of alkaloids


  • True (Typical) alkaloids: derived from amino acids and have nitrogen in a heterocyclic ring
  • Protoalkaloids: derived from amino acids and do not have nitrogen in a heterocyclic ring
  • Pseudo-alkaloids: not derived from amino acids but have nitrogen in a heterocyclic ring
  • False alkaloids: non alkaloids that give false positive reaction with alkaloidal reagents
• Alkaloid occurrence and distribution


  • Rare in lower plants
  • Dicots > Monocots
  • Families rich in alkaloids: Apocynaceae, Rubiaceae, Solanaceae, and Papavereacea
  • Families free from alkaloids: Rosaceae, Labiatae
  • Found in all plant parts e.g. Datura, barks e.g. Cinchona, seeds e.g. Nux vomica, roots e.g. Aconite, fruits e.g. Black pepper, leaves e.g. Tobacco, latex e.g. Opium
• Functions of alkaloids


  • Act as protectant against insects and herbivores
  • Final products of detoxification
  • Source of nitrogen
  • Act as growth regulators in certain metabolic systems
  • Can be utilized as a source of energy in case of deficiency in carbon dioxide assimilation
• Alkaloid properties


  • High biological activity
  • Produce varying degrees of physiological and psychological responses - largely by interfering with neurotransmitters
  • Others interfere with membrane transport, protein synthesis or other processes
  • In large doses - highly toxic – fatal
  • In small doses, many have therapeutic value e.g. muscle relaxants, tranquilizers, pain killers, mind altering drugs, chemotherapy
• Categories of psychoactive alkaloids


  • Stimulants
  • Hallucinogens
  • Depressants
• Although only a small percent of alkaloids are psychoactive, these get much focus
• Psychoactive alkaloids affect the central nervous system - often by influencing neurotransmitters
• Examples of psychoactive alkaloids


  • Stimulants: Cocaine, Ephedrine, Caffeine
  • Hallucinogens: Mescaline, Psilocybin, Ergot alkaloids (LSD)
  • Depressants: Morphine, Codeine, Heroin
• Alkaloid biosynthesis


  • Most alkaloids are synthesized from a few common amino acids (tyrosine, tryptophan, ornithine or argenine, aspartic acid, & lysine)
  • Nicotinic acid precursor for part of nicotine
  • Purine precursor for caffeine
  • Some alkaloids synthesized from terpenes - along mevalonic acid pathway
• Alkaloid naming conventions


  • Trivial names should end by "ine"
  • Named after the genus of the plant, the plant species, the common name of the drug, the name of the discoverer, the physiological action, or a prominent physical character
• Alkaloid prefixes and suffixes


  • Prefixes: "Nor-" designates N-demethylation or N-demethoxylation, "Apo-" designates dehydration, "Iso-, pseudo-, neo-, and epi-" indicate different types of isomers
  • Suffixes: "-dine" designates isomerism, "-ine" indicates lower pharmacological activity in case of ergot alkaloids
• Types of nitrogen in alkaloids

  • Primary amines - R -NH2 e.g. Norephedrine
  • Secondary amines - R2-NH e.g. Ephedrine
  • Tertiary amines - R3-N e.g. Atropine
  • Quaternary ammonium salts - R 4-N e.g d-Tubocurarine
• Alkaloid basicity


  • R2-NH > R-NH2 > R3-N
  • Weak bases e.g. Caffeine
  • Strong bases e.g. Atropine
  • Amphoteric alkaloids: Phenolic Alkaloids e.g. Morphine, Alkaloids with Carboxylic groups e.g. Narceine
  • Neutral alkaloids e.g. Colchicine
• Alkaloid extraction and purification methods


  1. Method I: Powder treated with alkalis to liberate free bases, then extracted with water immiscible organic solvents

  2. Method II: Powdered material extracted with water or aqueous alcohol containing dilute acid, alkaloids extracted as salts with impurities

  3. Method III: Powder extracted with water soluble organic solvents like MeOH or EtOH which dissolve both salts and free bases
• Alkaloid steam distillation


  Plant material + water + Fixed alkali heated, steam contains alkaloids received in acidic solution
• Alkaloid ring structures


  • Phenylalkylamines e.g. Ephedrine
  • Pyridine and piperidine e.g. lobeline, nicotine
  • Tropane e.g. Atropine
  • Quinoline e.g.quinine and quinidine
  • Isoquinoline e.g. papaverine
  • Phenanthrene e.g. Morphine
  • Indole e.g. ergometrine
  • Imidazole e.g. pilocarpine
  • Purine e.g. caffeine
  • Steroidal e.g. Solanum and Veratrum alkaloids
  • Terpenoid e.g. Taxol
• Examples of alkaloid-containing plants


  • Duboisa
  • Indian ginseng
  • Pyrrolizidine alkaloids
  • Piperidine alkaloids
  • Piperidine/Pyridine alkaloids
  • Betel nut
  • Black pepper
  • Pomengranate
  • Isoquinoline alkaloids
  • Ipecac
  • South American Arrow
  • Quinoline alkaloids
  • Indole alkaloids
  • Periwinkle
  • Snakeroot
  • Yohimbine
  • Calabar/Ordeal bean
  • Pilocarpus
  • Quinolizidine alkaloids
  • Steroidal alkaloids
  • Diterpenoid alkaloids
  • Amine alkaloids
  • Alkaloids without heterocyclic nitrogen atoms
  • Purine alkaloids
  • Betalain alkaloids - pigment alkaloids
  • Lycopodium alkaloids - restricted to club mosses
  • Peptide alkaloids
• Examples of specific alkaloid-containing plants


  • I. Areca/Areca Nut/Betel nut - Areca catechu, Constituents: arecoline, arecaidine, guvacine, guvacoline, Use: Anthelmintic
  • II. Lobelia/Indian Tobacco - Lobelia inflata, Constituent: Lobeline, Use: respiratory stimulant
  • III. Tobacco - Nicotiana tabacum, Constituent: Nicotine, Use: smoking deterrent
  • IV. Pepper - Piper nigrum, Constituent: Piperine, Use: tx gonorrhea/ chronic bronchitis
  • V. Pomegranate - Punica granatum, Constituent: Pelletierine, Use: Anthelmintic, Taenifuge, Vermifuge
  • VI. Poison Hemlock - Conium maculatum, Active Constituent: Coniine, Use: Antispamodic, sedative, anodyne
• Tropane alkaloids


  Derived from tropine and consist of mandelic, tropic or benzoic acid esters of tropine, very closely related
• Alkaloids


  • Pyrrolizidine alkaloids
  • Tropane alkaloids
  • Cinchona alkaloids
  • Opium alkaloids
  • Ergot alkaloids
  • Nux Vomica alkaloids
  • Alkaloid-like amines
  • Protoalkaloids
  • Purine alkaloids
• Areca/Areca Nut/Betel nut


  SN: Areca catechu, FN: Arecaceae, Constituents: arecoline, arecaidine, guvacine, guvacoline, Use: Anthelmintic
• Lobelia/Indian Tobacco


  SN: Lobelia inflata, FN: Lobeliaceae, Constituent: Lobeline, Use: respiratory stimulant → Used in asthma preparations
• Tobacco


  SN: Nicotiana tabacum, FN: Solanaceae, Constituent: Nicotine, Use: bound to ion exchange resin in chewing gum base (smoking deterrent), Product: Nicorette
• Pepper


  SN: Piper nigrum, FN: Piperaceae, Constituent: Piperine, Use/s: tx gonorrhea/ chronic bronchitis
• Pomegranate


  SN: Punica granatum, FN: Punicaceae, Constituent: Pelletierine, Use: Anthelmintic, Taenifuge, Vermifuge
• Poison Hemlock


  SN: Conium maculatum, FN: Apiaceae, Active Constituent: Coniine, Use/s: Antispamodic, sedative, anodyne
• Tropane alkaloids are derived from tropine and consist of mandelic, tropic or benzoic acid esters of tropine
• Tropane alkaloids are very closely related to each other and all have pronounced physiological actions
• Natural tropane alkaloids

  • Hyoscyamine
  • Hyoscine
  • Atropine
  • Cocaine
• The above mentioned tropane alkaloids occur within the Solanaceae family (except cocaine – from Erythroxylaceae family)
• Belladonna


  SN: Atropa belladonna, FN: Solanaceae, Constituents: atropine, 0.25% hyoscyamine – main, Use/s: Spasmolytic agent, antidote for physostigmine and organophosphate insecticides, mydriatic