Methylephedrine extractabilities

To improve supercritical C02 solubilities of target alkaloidal salts, an appropriate modifier to raise the polarity of C02 had to be used. As previously mentioned, the most common modifier used in SFE is methanol because of its high solvation parameters, which can greatly increase the resultant polarity of C02. Water has been chosen as another modifier because some alkaloidal salts are freely soluble in water as well as methanol. Moreover, the addition of water into C02 has been reported to improve the extraction yield of some alkaloids [29]. Methanol or water as a modifier was added into the extractor at the concentration levels of 1, 5 and 10% (v/v), respectively. The effect of methanol and water on the solubilities of hyoscyamine (1) and scopolamine (2) is shown in Figure 5. Analogous information on ephedrine derivatives such as methylephedrine (3), norephedrine (4), ephedrine (5), and pseudopehedrine is illustrated in Figure 6. 

Table 4. Yields of methylephedrine (ME), norephedrine (NE), ephedrine (E), and pseudoephedrine (PE) obtained by organic solvent extraction and SFE. Results are mg/g [41].u Reproduced with permission from Vieweg Publishing 1999.

Methylpentynol Bulk TLC extracted 50% EtOH (15 ml) RT, 30 min, centrifuged, filtered. ISTD-benzyltriethyl-ammonium chloride cm 75 ID, 28 kV Silica 0.005M barium hydroxide (pH 10) CHCI3-acctonc (4 1) KMnO, methylpseudo-ephedrine 5 min, pseudoephedrine 6.2 min, ephedrine 6.8 min, methylephedrine 7.8 min. norpseudoephedrine 8.1 min, norephedrine 8.8 min GC 2] [1]... 

Extracted ephedrine, ethylephedrine, N-methylephedrine, norephedrine, norpseudoephed-rine, pseudoephedrine... 

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. 

Typical Experimental Procedure Stirring a solution of an aldehyde and alkyne in toluene with 1.1 equiv Zn(OTf)2 and 1.2 equiv each of Et3N and (+)-A-methylephedrine, respectively, in toluene at 23°C for 2 to 20 hours furnishes adducts up to 99% e.e. (Table 21.4). Importantly, after the reaction is complete, the (+)-A-methylephedrine can easily be separated from the adducts by simple aqueous extraction (acid wash). 

Seven ephedrine alkaloids (synephrine, norephidrine, ephedrine, pseudoephi-drine, norpseudoephidrine, iV-methylephedrine, -methylpseudoephedrine) were extracted fiom various herbal formulations and baseline resolved on a phenyl column (A = 255nm). The use of a 98/2 water (0.1 M sodium acetate pH 4.8)/acetonitrile mobile phase resulted in a 14-min analysis. Synephrine eluted very close to the system void volume [1598]. Aworking curve from 4 to 150 pg/tnL was used and sample detection limits of 0.05 mg/g were reported. 

Phinney et al. developed three CE-UV methods that allowed the enantiose-paration of ephedrine and pseudoephedrine using neutral HP-pCD, DM-pCD, and charged sulfated pCD as chiral selectors. The combination of negatively charged sulfated pCD (2.8 %) and DM-pCD (1.2 %) under acidic conditions (pH 2.5) provided the best separation of the two couples of enantiomers. Standard reference materials (SRMs) containing ephedra in development at NIST were analyzed by each of three CE methods. In the SRM samples, only the naturally occurring enantiomers ( )-ephedrine and (-l-)-pseudoephedrine were found however, the method proved to be suitable in detecting product adulteration by its potential in identification of specific stereoisomers [56]. The neutral HP-pCD was also found to be a useful chiral selector in the presence of tetrabutylammonium chloride as additive, for the simultaneous enantioseparation of ephedrine, pseudoephedrine, iV-methylephedrine, and norephedrine enantiomers in Ephedra sinica extracts [57]. 

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