ALKALOIDS

SOURCES

Definition: Alkaloids are low molecular weight basic nitrogenous organic compounds containing nitrogen in a heterocyclic ring. In addition to C, H and N, most contains oxygen and some has sulphur too.

Gliotoxin (Aspergillus fumigatus)

Classification

Pseudoalkaloids are derived from terpenoids and purines.

Examples for Proto alkaloids

Hordenine

Ephedrine

Alkaloids from Amphibian Skin

J Nat Prod. 2005 Oct;68(10):1556-75. Alkaloids from amphibian skin: a tabulation of over eight-hundred compounds. Daly JW, Spande TF, Garraffo HM.

SALAMANDRA 46(1) 1115 20 February 2010 ISSN 00363375. Myrmecophagy and alkaloid sequestration in amphibians: a study on Ameerega picta (Dendrobatidae) and Elachistocleis sp. (Microhylidae) frogs

Dietrich Mebs1, Martin Jansen2, Gunther Khler2, Werner Pogoda1 & Gerold Kauert1

Mammalian Morphine 1976

Properties
Crystalline compounds Forms salt with acids Naturally exist in free state, N-oxides, salts, quaternary compounds, etc. Oxygen free and Liquid alkaloids

Coniine Nicotine

Solubility Sparingly soluble in water, soluble in organic solvents

Industrial process of Extraction and Purification

Mostly colourless, Some are coloured

Chemical Classification

Non-Heterocyclic alkaloids

Heterocyclic alkaloids

Non-Heterocyclic alkaloids

Hordenine
Mescaline

Ephedrine

Colchicine

Erythromycin

Pachysandrine

Paclitaxel

Heterocyclic Alkaloids
Me N N H N N H Pyrrolidine Tropane NH N N Isoquinoline NH Tetrahydroisoquinoline N H Indole N Imidazole N N N Quinoline

Piperidine Pyridine

NH

Purine

1. Pyrrole and Pyrrolidine

Stachydrine

2. Pyrrolizidine

Senesionine

Echimidine

3. Pyridine and Piperidine

Coniine

Nicotine

Pelletierine

Piperine

4. Tropane

5. Quinoline

Quinine

6. Isoquinoline

7. Aporphine 8. Nor-lupinane 9. Indole / Benzopyrrole 10. Indolizidine 11. Imidazole / Glyoxaline 12. Purine 13. Steroidal 14. Terpenoidal

7. Aporphine reduced isoquinoline / naphthalene

Boldine Source: Peumus boldus

8. Nor-lupinane

9. Indole / Benzopyrrole

10. Indolizidine

Castanospermine

11. Imidazole / Glyoxaline

Pilocarpine hydrochloride

12. Purine (Pyrimidine and Imidazole)

13. Steroidal alkaloids

Solanidine

14. Terpenoidal alkaloids

Atisine

Qualitative Chemical Tests

Dragendorff reagent(Potassium-bismuth-iodide solution) : Alkaloids give reddish-brown precipitate with this reagent.

Mayer reagent (Potassium-mercuric-iodide solution): Alkaloids gives cream colour precipitate with this reagent. Wagner reagent (iodine-potassium-iodide solution): Alkaloids give Brown colour precipitate with this reagent. Hager reagent (Saturated solution of picric acid): Alkaloids give yellow colour precipitate with this reagent. Tannic acid: - Alkaloids gives buff colour precipitate with this acid Picrolonic acid: - Alkaloids give yellow colour precipitate with this acid

Ephedra gerardiana (Ephedraceae)

Ain, Khanta, Somlata

Plant Description
Somlata is a low-growing rigid tufted shrub 1-2 ft tall, with numerous densely clustered erect slender, smooth, green, jointed branches, arising from a branched woody base. Branches have scales at the joints. Male cones are ovate, 6-8 mm, solitary or 2-3, with 4-8 flowers each with 5-8 anthers with fused filaments, and rounded fused bracts. Female cones are usually solitary. Fruit is ovoid 7-10 mm, with fleshy red succulent bracts enclosing the seeds. Goats and yaks feed on the branches during winter. Gerard Jointfir is found on stony slopes, gravel terraces and drier places in the Himalayas, from Afghanistan to Bhutan, at altitudes of 2400-5000 m. Flowering: May-June.

Ephedra alkaloids

Uses:
To relieve asthma and hay fever Action resembles adrenaline, but more prolonged Advantage: administered both orally and hypodermally Herb Sudorific

Root Antisudorific used clinically in China

Preparation
Ephedrine may be prepared by two methods, namely: (i) Fermentation method, and (ii) Synthetic method.

(a) Fermentation Method: It can be prepared commercially by fermenting a

mixture of molasses and benzaldehyde. The reaction product i.e., methyl benzyl alcohol ketone i.e., C6H5-CH(OH)COCH3, a keto-alcohol is subsequently mixed with a solution of methyl amine and freshly prepared H2-gas is made to pass though it. Thus, we have:

(b) Synthetic Method: Manske et al.(1929) synthesized ()-Ephedrine by the catalytic

reduction of 1-phenylpropane-1, 2-dione (or benzoylacetyl) in the presence of

methylamine in methanol solution as given below:

Special Features
(i) Ephedrine does not yield a precipitate with Mayers Reagent except in concentrated solution.

(ii) Ephedrine in chloroform solution after long standing or on evaporation usually forms ephedrine hydrochloride and phosgene.

(iii) Both ephedrine and pseudoephedrine are fairly stable to heat and when heated at 100C for several hours does not undergo any decomposition.

(iv) Ephedrine hydrochloride on being heated with 25% HCl gets partially converted to
pseudoephedrine; and this conversion is reversible and soon attains on equilibrium.

Identification Tests
(i) Colour Test: Dissolve 0.1 g ephedrine in 1 ml water with the addition of a few drops
of dilute HCl. Add to it two drops of CuSO4 solution (5% w/v) followed by a fewdrops of NaOH (1N) solution when a reddish colour is obtained. Add to it 2-3 ml of ether and shake vigorously, the ethereal layer becomes purple and the aqueous layer turns blue.

(ii) Formation of Ephedrine Hydrochloride: Dissolve 0.2-0.3g of ephedrine in 35 ml of

chloroform in a stoppered test tube and shake vigorously. Allow it to stand for 12 hours
and evaporate the chloroform, when crystals of ephedrine HCl are obtained.

(iii) Formation of Benzaldehyde Odour: Take 0.05 g of ephedrine in a small porcelain dish and triturate it with a few crystals of pure potassium ferricyanide, [K3Fe(CN)6], add a few drops of water and heat on a water-bath, it gives rise to a distinct odour of benzaldehyde.

ERGOT

Ergot of Rye (Secale cereale)

Figure 1a: Ergot (sclerotia) on rye. Ergot replaces grain of rye. Until 1850's the ergot was thought to be part of the plant.

Figure 1b: Ergot (sclerotia). The ergot is the over wintering stage and is also the part of the life cycle containing the alkaloids.

 Eating grain products contaminated with the fungus Claviceps purpurea cause ergotism.
The alkaloids can also pass through lactation from mother to child, causing ergotism in infants.

Convulsive symptoms include painful seizures and spasms, diarrhea, paresthesias, itching, mental effects including mania or psychosis, headaches, nausea and vomiting. Usually the gastrointestinal effects precede central nervous system effects.

The dry gangrene is a result of vasoconstriction induced by the ergotamine-ergocristine alkaloids of the fungus. It affects the more poorly vascularized distal structures, such as the fingers and toes. Symptoms include desquamation or peeling, weak peripheral pulses, loss of peripheral sensation, edema and ultimately the death and loss of affected tissues. Vasoconstriction is treated with vasodilators.

Identification:
Powdered ergot when treated with NaOH solution develops strong odour of triethylamine. Under UV light, it shows red colour.

Pharmacological uses
Ergot Alkaloids: Ergotamine (Ergomar) and Dihydroergotamine (Migranal)

Ergot alkaloids were the first antimigraine drugs available. Dihydroergotamine (DHE) is an ergotamine analog. DHE is administered as a nasal spray form (Migranal, Valeant Pharmaceuticals, QC, Canada) or by injection. Ergotamine (Ergomar, Rosedale Therapeutics, TN, USA) is available in oral and sublingual tablet formulation and rectal suppositories.