Alkaloids
Introduction
The term alkaloid (meaning “alkali-like”) refers to basic nitrogenous compounds of plant origin that are physiologically active. Over 21,000 alkaloids have been identified so far. They contain at least one nitrogen atom, are generally insoluble in water (but their salts are water-soluble), and are freely soluble in organic solvents like ether and chloroform.
The term “alkaloid” was coined by Meissner in 1819. The first alkaloid (norcotine) was isolated by Derosne in 1803, and morphine from opium was isolated by Serturner the same year. The first complete synthesis of an alkaloid (coniine) was achieved in 1886 by German chemist Albert Ladenburg.
Types of Alkaloids
A. True Alkaloids Derived from amino acids and contain a heterocyclic ring with nitrogen. Highly biologically active even in low doses. Primary precursors include L-ornithine, L-lysine, L-tryptophan, and L-histidine. Examples: Cocaine, Quinine, Dopamine, Morphine.
B. Proto/Amino Alkaloids The nitrogen atom from an amino acid is not part of a heterocyclic ring. Derived from L-tyrosine and L-tryptophan. Examples: Hordenine, Mescaline, Yohimbine.
C. Pseudo Alkaloids Not derived from amino acid precursors. Examples: Coniine, Capsaicin, Ephedrine, Caffeine, Theobromine.
Occurrence and Distribution
Alkaloids are found mainly in plants — especially the families Leguminosae, Papaveraceae, Ranunculaceae, Rubiaceae, Solanaceae, and Berberidaceae. They are also found in animals (musk deer), fungi (ergot alkaloids in Claviceps purpurea), insects, and bacteria.
Isolation of Alkaloids
Stas-Otto Process:
- Powdered material is defatted with non-polar solvents, moistened with water, and treated with ammonia to free the alkaloids.
- Extract is obtained using organic solvents (chloroform, ether) and concentrated.
- Dissolved in acid to form alkaloid salts, then basified with ammonia or sodium bicarbonate.
- Free alkaloids are collected from the organic phase and dried.
Manske’s Process:
- Powdered material is defatted and converted to methanol extract.
- Dissolved in water, acidified to pH 2, and allowed to stand in a refrigerator or treated with boiling paraffin.
- Filtrate is shaken with organic solvent and basified with ammonia.
- Free alkaloids collected and dried.
Identification Tests for Alkaloids
| Reagent | Result |
|---|---|
| Mayer’s Reagent (Potassiomercuric iodide) | Cream-coloured precipitate |
| Wagner’s Reagent (Iodine in KI solution) | Brown or reddish-brown precipitate |
| Hager’s Reagent (Picric acid solution) | Yellow precipitate |
| Dragendroff’s Reagent (Potassium bismuth iodide) | Reddish-brown precipitate |
| Murexide Reagent (Ammonium purpurate) | Purple precipitate |
Therapeutic Applications of Alkaloids
- CNS Depressants: Morphine
- CNS Stimulants: Caffeine
- Sympathomimetic: Ephedrine
- Parasympathomimetic: Pilocarpine
- Anticholinergic: Atropine, Hyoscyamine
- Local Anaesthetic/Analgesic: Cocaine, Morphine
- Antitumor: Vinblastine
- Antimalarial: Quinine
- Antibacterial: Berberine
- Antiseptic: Scopolamine
Glycosides
Introduction
A glycoside is a molecule in which a sugar group is bonded through its anomeric carbon to another group via a glycosidic linkage. The sugar component is called the glycone and the non-sugar component is called the aglycone (or genin). Both parts can be separated by hydrolysis in the presence of acid or enzymes. The aglycone is the pharmacologically active part of the glycoside.
Classification of Glycosides
By glycosidic linkage:
- O-glycoside — sugar bonded to a phenol or OH group. Examples: Amygdalin, Salicin, Arbutin.
- N-glycoside — sugar bonded to an amine group. Example: Nucleosides.
- S-glycoside — sugar bonded to a thiol group. Example: Sinigrin.
- C-glycoside — sugar bonded to a carbon atom. Examples: Aloin, Barbaloin.
By aglycone nature:
- Cardiac/Sterol glycosides — Digitalis, Squill
- Anthraquinone glycosides — Senna, Aloe, Rhubarb
- Saponin glycosides — Liquorice, Ginseng
- Flavone glycosides — Ginkgo
- Phenol glycosides — Cascara, Bearberry
- Thiocyanate glycosides — Black Mustard
- Aldehyde glycosides — Vanilla
- Steroidal glycosides — Solanum
Identification Tests for Glycosides
| Test | Glycoside Type | Positive Result |
|---|---|---|
| Borntrager’s Test | Anthraquinone | Pink/red colour in ammonia layer |
| Saponin Test | Saponin | Rupture of RBCs |
| Killer-Killani Test | Cardiac | Reddish-brown layer turning bluish-green |
| Vanillin HCl Test | Flavonoid | Pink colour |
| Steroid Test (H₂SO₄) | Steroid | Yellow ring turning red |
Therapeutic Applications of Glycosides
- Senna — Laxative; stimulates smooth muscles of the large intestine.
- Aloe — Purgative and vermifuge; acts on the large intestine.
- Digitalis — Treats heart disease; allows the heart to beat more slowly, powerfully, and regularly.
- Bitter Almond — Used as a sedative.
Volatile Oils and Terpenoids
Introduction
Volatile oils (also called essential oils) are odorous chemical substances that evaporate easily at ordinary temperature. They represent the essence of the plant’s active constituents. Unlike fixed oils, they are freely soluble in ether and chloroform, sparingly soluble in alcohol, and insoluble in water. They are colorless liquids that darken on exposure to air and sunlight due to oxidation.
Classification of Volatile Oils (by chemical nature)
| Class | Examples |
|---|---|
| Hydrocarbons | Turpentine oil |
| Alcohols | Sandalwood oil, Peppermint oil |
| Ketones | Caraway, Dill, Fennel, Camphor |
| Aldehydes | Lemongrass oil, Cinnamon oil, Saffron |
| Phenols | Clove, Ajowan, Tulsi |
| Phenolic Ethers | Nutmeg, Calamus |
| Oxides | Cardamom, Eucalyptus, Chenopodium oil |
| Esters | Rosemary oil, Garlic, Gaultheria oil |
Terpenoids
Terpenoids are hydrocarbons of plant origin with the general formula (C₅H₈)n, along with their oxygenated, hydrogenated, and dehydrogenated derivatives. The term “terpene” originates from turpentine, a volatile liquid from pine trees.
| Type | Carbon Count | Examples |
|---|---|---|
| Monoterpene | C10 | Essential oils, oleoresins, pyrethrins |
| Sesquiterpene | C15 | Essential oils, sesquiterpenoid lactones |
| Diterpene | C20 | Retinol |
| Triterpene/Steroids | C30 | Saponins, cardiac glycosides |
| Tetraterpene | C40 | β-Carotene |
Isolation Methods for Volatile Oils
- Distillation — Hydrodistillation or steam distillation, the most widely used method.
- Scarification — Used for citrus peel oils (lemon, orange, bergamot) by two processes:
- Sponge Process — Oil glands burst open and oil is absorbed by a sponge, then separated from water.
- Écuelle Process — Rinds are ruptured mechanically using pointed projections; oil is collected.
Identification Tests for Volatile Oils
- Treatment with alcoholic Sudan-III solution develops a red colour.
- Treatment with tincture of alkanna produces a red colour.
- Addition of 1% FeCl₃ to eugenol-containing drug gives a green colour.
Colour-based identification with FeCl₃:
- Yellow → Menthol
- Green → Thymol or Eugenol
- Violet → Methyl salicylate
- Dark blue → Vanillin
Therapeutic Applications of Volatile Oils
- Flavoring and perfuming agents in pharmaceutical formulations to mask unpleasant odors
- Used in food, beverages, and cosmetics industries
- Carminative — Umbelliferous fruits (Coriander, Fennel)
- Irritant — Turpentine, Oil of Wintergreen
- Local Anaesthetic — Clove oil
- Sedative — Jatamansi
- Anthelmintic — Chenopodium oil
Tannins
Introduction
Tannins are complex, non-nitrogenous, phenolic plant secondary metabolites with astringent properties. The term was first used by Seguin in 1796 to describe substances that convert animal hides into leather — a process known as tanning. Detection is done using the Goldbeater’s Skin Test.
Classification of Tannins
Pseudo Tannins — Partly retained by hide powder; fail the Goldbeater’s test.
True Tannins — Give a positive Goldbeater’s test. Further divided into:
- Hydrolysable (Pyrogallol) Tannins — Easily hydrolysed by mineral acids or enzymes. Polyphenolic acids are bound via ester linkages to a central glucose molecule. Subdivided into:
- Gallotannins — composed of gallic acid
- Ellagitannins — composed of hexahydrodiphenic acid
- Non-hydrolysable (Condensed/Proanthocyanidin) Tannins — Resistant to hydrolysis. Biosynthetically related to flavonoids and contain condensed phenolic nuclei.
Identification Tests for Tannins
- Goldbeater’s Skin Test — Skin soaked in HCl and placed in tannin solution; transferred to FeSO₄ solution → brown/black membrane = positive.
- Phenazone Test — Tannin solution + sodium acid phosphate + phenazone → bulky colored precipitate.
- Gelatin Test — Tannin solution added to gelatin + NaCl → precipitation of gelatin.
Therapeutic Applications of Tannins
- Astringent properties that promote rapid wound healing and new tissue formation
- Treatment of wounds and inflamed mucosa
- Used for ulcers, hemorrhoids, minor burns, and frostbite
- Recent studies show antiviral activity, including potential use in treatment of AIDS
Resins
Introduction
Resins are complex, amorphous, more or less solid substances that soften and melt on heating. They are insoluble in water and petroleum spirit but dissolve in alcohol, chloroform, and ether.
Classification of Resins
By chemical nature (functional group):
- Resin Acids — Contain carboxylic acid groups; used in soaps, paints, and varnish industries.
- Resin Esters — Esters of resin acids with aromatic acids (benzoic, cinnamic, salicylic).
- Resin Alcohols (Resinols) — High molecular weight alcoholic compounds.
- Resin Phenols (Resinotannols) — High molecular weight phenolic compounds.
By association with other chemicals:
- Glucoresins — Resin combined with sugar by glycosylation.
- Oleoresins — Homogeneous mixture of resin and volatile oils. Example: Turpentine.
- Gum Resins — Natural mixture of resin and gum. Example: Myrrh.
- Oleogum Resins — Natural mixture of resin, volatile oil, and gum. Example: Asafoetida.
- Balsams — Resinous mixtures containing a high proportion of aromatic acids (benzoic and cinnamic acids). Example: Tolu Balsam, Benzoin.
Identification Tests for Resins
- Dissolve in acetic anhydride + concentrated H₂SO₄ → purple colour rapidly changing to violet.
- Boil with HCl, filter, add ammonia → blue fluorescence.
- Add 50% nitric acid → green colour.
- Add 1 drop of H₂SO₄ → red colour changing to violet on washing with water.
- Alcoholic balsam solution + potassium permanganate → benzaldehyde produced.
- Alcoholic balsam solution is acidic to litmus paper.
Therapeutic Applications of Resins
- Local irritant and cathartic — Jalap, Ipomoea
- Anticancer — Podophyllum
- Bronchial asthma — Cannabis
- Mild antiseptic — Benzoin (tinctures)
- Ointments and plasters — Turpentine, Colophony
- Used in preparation of emulsions and sustained-release formulations
D.Pharma 1st Year — All Subjects Notes
D.Pharma 2nd Year — All Subjects Notes