Z Ephedrine

For commercial Ephedra the British Pharmaceutical Codex, 1934, specifies a total alkaloidal content of not less than 1-25 per cent, when assayed by the method therein prescribed. The proportion of Z-ephedrine is generally about 70 per cent. Methods of assay for total alkaloids are described by Feng and Read and by Krishna and Chose, who discuss the various difficulties involved and comments on these and other methods have been made by various workers. Conditions affecting the results of such assays have also been discussed by T ang and Wang, and Brownlee has shown that chloroform is not a suitable medium for the assay since it converts ephedrine quickly and 0-ephedrine slowly to the hydrochloride. 

On boiling with 25 per cent, hydrochloric acid cphedrine is partially converted into -ephedrine. This change is reversible, an equilibrium mixture of the two bases being formed, though according to Mitchell the commercially desirable conversion of 0-ephedrine into Z-ephedrine is effected with more difficulty than the reverse process. Mitchell also states that when ephedrine is heated with acetic anhydride at 70° for ten minutes it is converted into 0-acetylephedrine,. 2H2O,... 

The (ZZ-ephedrine was resolved into its components by the use of d-and Z-mandelic acids. In 1921 Neuberg and Hirsch showed that benz-aldehyde was reduced by yeast, fermenting in suerose or glueose solution to benzyl aleohol and a phenylpropanolone, which proved to be Z-Ph. CHOH. CO. CH3. This ean be simultaneously, or consecutively, eondensed with methylamine and then eonverted to Z-ephedrine by reduction, e.g., with aluminium amalgam in moist ether, or by hydrogen in presenee of platinic oxide as catalyst (Knoll, Hildebrant and Klavehn ). 

The thought that transmethylation of noradrenaline may be an initial step in its deactivation in the body makes one wonder whether further transmethylation of adrenaline is also not a common biological process. As a result of studies of the various alkaloids of plants of the Ephedra species, it was noted that not only Z-ephedrine and its stereoisomer d-pseudoephedrine are present but also that -norephedrine, d-norpseudoephedrine, l-methylephedrine, and d-methylpseudoephedrine (8) are present. The quaternary tri-methylammonium compounds corresponding to these were not reported but very... 

Efhedrine (Jl) is an alkaloid of the Chinese medicinal herb Ma Huang which has been identified as Ephedra sinica Stapf (14), and it also occurs in the leaves of the yew, Taxus baccata L. (15). The natural base is the Z-isomer. The Chinese plant contains small amounts of several closely related alkaloids d-pseudoephedrine, d-norpsevdoephedrine (III), l-methyl-ephedrine (IV), and d-methylpseudoephedrine. d-Pseudoephedrine is a diastereoisomer but not an enantiomorph of Z-ephedrine. 

Spehr (154) gave the name ephedrine to a base isolated from E. monostachia of unknown botanical authority, but the compound is chemically and physiologically different from Z-ephedrine. The base, C13H19ON, melted at 112°, was freely soluble in water and yielded a hydrochloride melting at 207°. 

Ephedrine and Z -ephedrine are quite stable compounds. Heating at 100° for 24 hours causes no decomposition (42, 28). No alteration is observed by heating the bases with 5% sodium hydroxide on the water bath (21). Unsuccessful attempts were made to racemize ephedrine and Z -ephedrine with barium hydroxide or alcoholic potassium hydroxide... 

Structure I contains two dissimilar asymmetric centers so that four optically active isomers and two racemic forms are possible. The naturally occurring Z-ephedrine and d-iZ -ephedrine are not optical antipodes, but mutually interconvertible diastereoisomers. The other possible forms are known only as synthetic compounds. 

The toxicities of ephedrine and i -ephedrine were compared by Fujii, who found that the latter is less toxic in frogs but more toxic in mice. Pak and Read showed that -ephedrine is less toxic than ephedrine in frogs, rats, rabbits and dogs the reverse is true in hamsters. Chen, Wu, and Henriksen found that the M. L. D. expressed in mg./kg. body weight, in white rabbits was . Z-ephedrine 60 dZ-ephedrine 60 d-ephedrine 80 d- Z -ephedrine 75 dZ- Z -ephedrine 70 Z-iZ -ephedrine 80 norephedrine 70. The natural tertiary amine, Z-methylephedrine was proved to be much less active than ephedrine. 

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