D-i/ -Ephedrine

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. 

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]

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

Only a few compounds containing only one phosphinite group have been used successfully in catalytic reactions, e.g., EphosNH, 56. This compound was obtained from (+ )-ephedrine and (dimethylamino)diphenylphosphine by a simple exchange reaction of the dimethylamino group55 and used in asymmetric hydroformylation (Section D.I.5.8.). 

The pharmacological action of the natural alkaloid is similar to that of ephedrine (18). The racemic synthetic compound had already been examined by Barger and Dale. Hyde, Browning, and Adams prepared a series of homologues of d,2-ephedrine, in which the alkyl group on the jS-carbon was replaced by H, ethyl, and n-propyl. The only homologue that gave a dependable increase in blood pressure was the a-phenyl-/3-methylaminoethanol, i.e., racemic halostachine (20). 

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. 

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. 

Comparative investigations on the stereoisomerides of ephedrine, made by Fujii (301), Pak and Read (302), Chopra, Dikshit and Pillai (303, 304, 305), Chen, Wu and Henriksen (306) and others, showed that they have similar pharmacological effects to those of ephedrine, but differ in some particular direction and intensity of action. Compared indirectly with adrenaline, in pithed cats, i-ephedrine is about three times stronger than d-ephedrine. f-Ephedrine is five times as potent as d- -ephedrine, which is seven times as potent as f- -ephedrine (307). Pak and Read, by direct comparison in anesthetized dogs, found that f-ephedrine is twice as effective as d- -ephedrine. 

According to Chen, Wu, and Henriksen, norephedrines have a strong action, comparable to that of the ephedrines nor-d- -ephedrine has a weaker action than I or dl-ephedrine, but stronger than d- f -ephedrine. 

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. 

The most successful modifier is cinchonidine and its enantiomer cinchonine, but some work in expanding the repertoire of substrate/modifier/catalyst combinations has been reported (S)-(-)-l-(l-naphthyl)ethylamine or (//)-1 -(I -naphth T)eth Tamine for Pt/alumina [108,231], derivatives of cinchona alkaloid such as 10,11-dihydrocinchonidine [36,71], 2-phenyl-9-deoxy-10, 11-dihydrocinchonidine [55], and O-methyl-cinchonidine for Pt/alumina [133], ephedrine for Pd/alumina [107], (-)-dihydroapovincaminic acid ethyl ester (-)-DHVIN for Pd/TiOz [122], (-)-dihydrovinpocetine for Pt/alumina [42], chiral amines such as 1 -(1 -naphtln I)-2-(I -pyrro 1 idiny 1) ethanol, l-(9-anthracenyl)-2-(l-pyrrolidinyl)ethanol, l-(9-triptycenyl)-2-(l-pyrrol idi nyl)cthanol, (Z )-2-(l-pyrrolidinyl)-l-(l-naphthyl)ethanol for Pt/alumina [37,116], D- and L-histidine and methyl esters of d- and L-tryptophan for Pt/alumina [35], morphine alkaloids [113],... 

High degrees of enantioselectivity have been observed when alkylzinc reagents react with aldehydes in the presence of chiral ligands.120 Among several compounds that have been used as ligands are exo - (dime th y I a m i no )no rb o rn c o I (A)121 122 123 124 and diphenyl(l-methyl-pyrrolin-2-yl)methanol (B) as well as ephedrine derivatives C and D. 

Methyldopa [Aldomet) [Antihypertensive/Centrally Acting Antiadrenergic] Uses HTN Action Centrally acting antihypertensive Dose Adults. 250-500 mg PO bid-dd (max 2-3 g/d) or 250 mg-1 g IV q6-8h Peds. 10 mg/kg/24 h PO in 2-3 + doses (max 40 mg/kg/24 h - q6-l2h) or 5-10 mg/kg/dose IV q6-8h to total dose of 20—40 mg/kg/24 h i in renal insuff/elderly Caution [B (PO), C (IV), +] Contra Liver Dz MAOIs Disp Tabs, inj SE Discolors urine inidal transient sedadon/drowsiness frequent, edema, hemolydc anemia, hepadc disorders Interactions T Effects W/ anesthetics, diuredcs, levodopa, Li, methotrimeprazine, thioxanthenes, vasodilators, verapamil T effects OF haloperidol, Li, tolbutamide 1 effects W7amphetamines, Fe, phenothiazine, TCAs 1 effects OF ephedrine EMS Use diuredcs, verapamil, and sympathomimedcs w/ caudon may T risk hypotension, arrhythmias and pressors effects OD May cause profound hypotension, drowsiness, and impaired myocardial conduction activated charcoal may be effective... 

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