I- Ephedrine

The world war made all these sources of supply difficult of access and stimulated interest in the possibilities of local production. Examination of a number of American species of ephedra had already shown them to be devoid of alkaloids, except for the S. American species E. andina, in which Chavezt found ephedrine, and in the United States attention has been given to the experimental cultivation of imported species, notably E. sinica and E. gerardiana a Moroccan type, E. alenda, was found to contain only ). In Australia experimental cultivation of the Indian species E. gerardiana, E. intermedia and E. nebrodensis has been tried and preliminary yields of 1-35, 1-OS and 0-98 per cent, of total alkaloids respectively have been recorded. In Russia, E. equisetina and E. intermedia are available and are considered to be worth exploitation. In Italy various local species have been found to contain mainly i -ephedrine and that in small amount, but better results are recorded for two species already referred to and which are available in Sardinia, viz. E. vulgaris Rich and E. nebrodensis. ... 

Attempts had been made from 1904 onwards to synthesise ephedrine or ephedrine-like substances, but it was not imtil 1920 that two substances now generally accepted as optieally inactive forms of ephedrine and i/i-ephedrine were obtained by Eberhard. The proeess used was the reduetion of a-methylaminopropiophenone by (a) sodium amalgam and dilute hydrochloric acid and (b) hydrogen in presenee of palladised ehareoal ... 

The first product in the Spath and Gohring synthesis is d/-i/i-ephedrine, m.p. 118-9°, which was resolved, by crystallisation of the d-tartrate and Z-tartrate in succession, into Z- and [Pg.641]

The Wenker synthesis is not stereospecifio when the hydroxyl group of the amino alcohol is on benayhtypo carbon atom. t-Ephr-drine erythro) (XIX) and i -ephedrine (XVUla) give the... 

I -Ephedrine (= R, 2S)-1 -Phenyl-1 -hydroxy-2-methylaminopropane) (phenylpropanoid amino alcohol)... 

Methylenetiiphenylphosphorane, 307 Methylenomycin A, 183 Methylenomycin B, 184 N-Mcthylephedrine, 308 N-Methyl-i//-ephedrine, 421 Methyl fluorosulfonale, 302, 307 (+)-(S)-4-Methyl-3-heptanone, 17 Methyl 3-hydroxybutyrate, 406 Methyl hydroxymethoxyacetate, 19, 20 Methyl hypobromite, 501 Methyl iodide, 308-309 5-Methylisoxazole, 309 3-Methyl-5(4/0-isoxazolone, 309 Methyl jasmonate, 92, 358 Methylketene methyl trimethylsilyl acetal, 310... 

The reaction is also convenient for synthesis of acyclic -amino alcohols. Thus reaction of 1 with benzaldehyde followed by reduction gives a mixture of ( )-ephedrine (2,erylhro) and ( )-i -ephedrine (3, threo) in the ratio 3.3 1. The opposite stereoselectivity obtains when the reaction is used to prepare a tertiary amino alcohol. Thus the same sequence applied to 4 leads mainly to the threo-isomer (5, N-methyl-i r-ephedrine). 

E.J. Valente, J. Zubkowski, D.S. Egglestron, Discrimination in resolving systems I ephedrine-mandelic acid. Chirality 4 (1992) 494—504. 

Salts of 2-carboxyphenoxatellurin with nor-c -i -ephedrine, strychnine, cinchonidine, quinine, and r/-a-phenylethylamine were prepared with the hope of resolving 2-carboxyphenoxatellurin into optically active isomers. 2-Carboxyphenoxatellurin samples regenerated from these salts did not have optical activity b 2-Carboxyphenoxatellurin was esterified by heating with /-menthol . 

All substances included in Tables 1 and II All substances included in Table I Ephedrine, pseudoephedrine... 

The optical yield of the oxirane obtained using (1) is 67%. If the asymmetric salt (2) derived from i//-ephedrine is used, the enantiomeric oxirane is formed preferentially. This striking asymmetric synthesis can be achieved with only 0.2 eq. of the catalyst. The choice of solvent is also important. Little asymmetric induction is observed with THF or acetonitrile as solvent use of benzene, however, results in a high degree of induction. 

We turn now to a consideration of the actual orientations at C.9 in the cinchona bases. Of the arguments which may be presented (156, 157), that which correlates the alkaloids with (—) ephedrine (CXXVII) and (-I-) -ephedrine (CXXVIII) (158-161) appears to us the sounder. 

Several bases, other than ephedrine and i -ephedrine, have been identified in Ma Huang. Smith found 1-iV-methylephedrine (146) and nor-d-i -ephedrine (147) in the sirupy alkaloidal residue obtained in the manufacture of ephedrine. Nagai and Kanao (149), working up thoroughly a Ma Huang extract, confirmed Smith s observations and separated another new alkaloid, d-A-methyl- f -ephedrine. Kanao (150) succeeded in isolating a sixth ephedra base, 1-norephedrine. 

Ephedrine occurs also in the Papaveraceae, Roemeria refracta D.C., as shown by Knovalova, Yunusov and Orekhov (161) and has been recognized in the so called amorphous aconitine, which is a mixture of residual bases obtained in the commercial preparation of crystalline aconitine from Aconitum napellus L. (162). Freudenberg and Roger s previous statement (163), that i -ephedrine is a degradation product of the napellus alkaloids, has therefore to be revised. 

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