Norephedrine agent

Acylation of norephedrine (56) with the acid chloride from benzoylglycolic acid leads to the amide (57), Reduction with lithium aluminum hydride serves both to reduce the amide to the amine and to remove the protecting group by reduction (58), Cyclization by means of sulfuric acid (probably via the benzylic carbonium ion) affords phenmetrazine (59), In a related process, alkylation of ephedrine itself (60) with ethylene oxide gives the diol, 61, (The secondary nature of the amine in 60 eliminates the complication of dialkylation and thus the need to go through the amide.) Cyclization as above affords phendimetra-zine (62), - Both these agents show activity related to the parent acyclic molecule that is, the agents are CNS stimulants... 

Ephedrine, for example, produces weak AMPH-like activity (Huang and Ho 1974b). (+)Norpseudoephedrine (cathine) also produces AMPH-like stimulus effects. The oxidized analogs of norephedrine and ephedrine, cathinone and methcathinone, respectively, however, are potent AMPH-like agents (table 2). 

Pseudoephedrine and phenylpropanolamine [( )-norephedrine] are sympathomimetic agents with actions similar to those of ephedrine and are most commonly used for the relief of nasal congestion (363). Pseudoephedrine has been stated to have less pressor activity and central nervous system effects than ephedrine. 

In a broad program of using chiral oxazolidinones in asymmetric synthesis,100 Evans s group published a paper in 1992 on the synthesis and utilization of fV-sulfinyl oxazolidinones as new sulfinylating agent.87 Two chiral auxiliaries were used in the study oxazolidinones derived from (4R, 5S)-norephedrine 74101 and (45)-phenylalanine 75.102 The corresponding fV-sulfinyl oxazolidinones 77 and 78 were obtained either by sulfmylation of the metallated oxazolidinone or by oxidation of the derived N-sulfenamides (Table 15). 

Based on the observation that the best ee is obtained with bifunctional chiral agents (ephedrine, pseudoephedrine, norephedrine, and valinol see Scheme 43), we tentatively conclude that a multipoint interaction between the reactant molecule, the chiral inductor, and the zeolite interior is necessary to induce preferential adsorption of tropolone alkyl ether from a single enantiotopic face. The dependence of chiral induction (% ee) on the nature of cations (Scheme 45) suggests a crucial role of the cation present in the supercages in the chiral induction process. This is further strengthened by the results observed with wet and dry zeolites. The presence of water decreases chiral selectivity (Scheme 45). Water molecules... 

Placebo-controlled comparative trials with phenylpropanolamine, norfenefrine, and norephedrine support the modest efficacy of these agents in mild or moderate SUL These agents have been found to variably affect maximum urethral closure pressure and functional urethral length. 

All ephedra plants contain phenylalanine-derived alkaloids. These include (-)-ephedrine, (+)-pseudoephedrine, (-)-norephedrine, (+)-norpseudo-ephedrine (also called cathine because it is a major alkaloid of Catha edulis or khat, a plant used as a stimulant in North Africa), (-)-A-methylephedrine and (+)-A-methylpseudoephedrine, (+)-pseudoephedrine, and (+/-)-norephedrine (phenylpropanolamine). Significant enantioselective differences with regard to both pharmacokinetic and pharmacodynamic effects of these agents are possible. All of these alkaloids have important effects on the cardiovascular and respiratory systems, but not to the same degree. 

The p-position has not been particularly well investigated. Perhaps the best-studied derivatives are ephedrine and norephedrine—and even these agents have not been especially well investigated. Ephedrine and norephedrine are phenylpropanolamines that may be viewed as the p-hydroxy analogues of methamphetamine and amphetamine, respectively. Actually, p-hydroxylation of amphetamine or methamphetamine results in the creation of a new chiral center hence, a total of four optical isomers result from hydroxylation in each case. These eight structures are shown in Figure 23.3. Relatively little comparative information is available regarding the central stimulant actions of these phenylpropanolamine isomers. 

Although SDS is the most versatile and useful micellar agent, different surfactants can be introduced in MEKC to gain specific selectivity. Interestingly, Hou et al. performed the simultaneous MEKC enantioseparation of four pairs of ephedrine related compounds, namely, ( )-ephedrine, ( )-pseudoephedrine, ( )-norephedrine, and ( )-A-methylephedrine, using a polymeric chiral surfactant, i.e., polysodium A-undecenoxycarbonyl-L-leucinate. Because of the high molecular mass of the surfactant, the BGE showed to be compatible with the online ESI-MS detection [91]. In Fig. 36.6, the effect of the chiral surfactant concentration on the separation of the studied analytes is shown. 

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