A. Ephedrine:
Biological Source It is obtained from the dried tender stems of the Chinese wonder drug Ma Huang which is being used in the Chinese systems of Medicine for more than five thousand years. It occurs in Ephedra vulgaris Hook. F. (E. gerardiana Wall); Ephedra sinica Stapf. (1-3%); Ephedra equisetina Bunge. (2%) belonging to the natural order Gentaceae; and several other Ephedra species. Besides, it is also found in the roots of Aconitum napellus L. (Ranunculaceae) (Aconite, Monkshood, Blue Rocket); and Ephedra nevadensis S. Wats. (Ephedraceae) (Mormon Tea, Nevada Jointfir).
Chemical Structure
α-[1-(Methylamino)-ethyl] benzene-methanol; (C10H15NO).
Isolation Both ephedrine and pseudoephedrine may be extracted from the plant source by general procedures described earlier under alkaloid extraction, through successive and dilute HCl extraction procedures.
However, the separation of ephedrine from pseudoephedrine may be accomplished by means of their corresponding oxalate salts; the ephedrine oxalate being comparatively less soluble in cold water than pseudoephedrine oxalate separates out first.
Note: Chloroform is not ragarded as an appropriate solvent for extraction of ephedrine as it forms its corresponding ephedrine hydrochloride salt after its dissolution in CHCl3 and subsequent evaporation of solvent.
Fermentation Method Ephedrine may be prepared on a commercial scale economically by the process of fermentation using a mixture of molasses (a by-product of sugar industry containing 8-10% of cane sugar i.e., C6H12O6) and benzaldehyde. The resulting keto-alcohol i.e., benzylhydroxy methyl ketone is subsequently mixed with a solution of methylamine and treated with hydrogen gas to yield a racemic mixture of ephedrine as given below:
Characteristic Features The characteristic features of some racemic forms, optical isomers and their respective salts are enumerated below:
1. dl-Ephedrine (Synonyms: Racephedrine; Racemic Ephedrine): The crystals have mp 79°C; and are soluble in oils, chloroform, ether, water, and ethanol.
2. dl-Ephedrine Hydrochloride (Synonyms: Ephetonin; Racephedrine Hydrochloride) (C10H15NO.HCl): The crystals have mp 187–188°C; and pH 6.0. Its solubility profile are: 1 g dissolves 4 ml water, 40 ml of 95% ethanol at 20°C; and practically insoluble in ether.
3. dl-Ephedrine Sulphate (Synonym: Racephedrine Sulphate) (C10H15NO.H2SO4): The crystals have mp 247°C, and are soluble in ethanol and water. Its solution has a pH of 6.0.
4. l-Ephedrine [L-Erythro-2(methylamino)-1-phenylpropan-1-ol): It is obtained as waxy solid, crystals or granules, having a soapy feel and the substance gradually decomposes on exposure to light. It may contain water upto ½ mole (5.2%). However, the anhydrous product is hygroscopic in nature having mp 34°C. Interestingly, the absorption of water enhances mp to 40°C; and bp 255°C. The pH of aqueous solution (1 in 200) is 10.8. 1 g of it dissolves in 20 ml water, 0.2 ml ethanol; and freely soluble in ether, chloroform and oils.
5. l-Ephdrine Hydrochloride (Synonyms: Ephedral; Senedrine): It is obtained as orthorhombic needles having mp 216-220°C, which are affected by light. Its specific optical rotation [α]D25 -33 to –35.5° (C = 5). The pH of aqueous solution (1 in 200) is 5.9. 1 g dissolves in 3 ml water, 14 ml ethanol; and is found to be practically insoluble in chloroform and ether.
6. l-Ephedrine Sulphate: Its orthorhombic needles have mp 245°C (decomposed) and are affected by light. Its specific optical rotation [α]D25 -29.5 to –32.0° (C = 5). 1 g dissolves in 1.2 ml water and 95 ml ethanol; and freely soluble in hot alcohol. Its pH is about 6.
Identification Tests
1. Dissolve 0.01 g of ephedrine in 1 ml water by adding a few drops of dilute HCl. To this add two drops of CuSO4 solution (5% w/v) followed by a few-drops of NaOH solution when a reddish colour is developed. Now, add 2-3 ml ether and shake the contents thoroughly; the ethereal layer turns purple while the lower aqueous layer becomes blue.
2. Dissolve 0.2 g of ephedrine in 30 ml of chloroform in a stoppered flask and shake the contents vigorously. Allow the mixture to stand for at least 12 hours at room temperature and then remove the chloroform over an electric water bath. The crystals of ephedrine hydrochloride separate out.
3. Triturate 0.05 g of ephedrine with a few crystals of [K3Fe(CN)6] i.e., potassium ferricyanide, followed by a few drops of water and heat on a water bath slowly when a distinct odour of benzaldehyde (i.e., similar to the odour of bitter almonds) in given out.
Uses
l. l-Ehedrine is used extensively as a bronchodilator.
2. It also exerts excitatory action on the CNS and produces noticeable effects on skeletal muscles.
3. It is also employed as nasal decongestant.
