Ephedrine applications

With Phenylpropanolamine at hand (or ephedrine and pseudo-ephedrine) one would next need to reduce that alpha carbon OH group to get the final amine. Strike understands that the current favorite methods for doing this involve lithium and amine. HI and red P or other iodine related protocols. So when you meth heads ruin every aspect of those methods as well, what will you do then The following are a couple of OH reduction methods (Strike thinks) that have applicable use [99-100]. 

In the same study, these authors have prepared another series of amino-sulf(ox)ide ligands based on the (Nor)ephedrine and 2-aminodiphenylethanol skeletons, bearing two chiral centres in the carbon backbone.Their application to the iridium-catalysed hydrogen-transfer reduction of acetophenone generally gave better yields, but the enantioselectivity never exceeded 65% ee (Scheme 9.4). 

Several examples exist of the application of chiral natural N-compounds in base-catalyzed reactions. Thus, L-proline and cinchona alkaloids have been applied [35] in enantioselective aldol condensations and Michael addition. Techniques are available to heterogenize natural N-bases, such as ephedrine, by covalent binding to mesoporous ordered silica materials [36]. 

Ephedrine is the main alkaloid produced in the roots of Ephedra sinica, preparations of which have found medical application in China for at least 5000 years. It was first purified from its natural source in 1887, and its chemical synthesis was achieved in 1927. It was initially used in cardiovascular medicine, but subsequently found wider application in the treatment of mild hayfever and asthma. It is also used as a nasal decongestant and cough suppressant. 

Several other 8-hydroxynitrosamines have been or are likely to be found in environmental samples. Among these are N-nitroso-3-hydroxypyrrolidine X (l ) (found in bacon), N-nitrosobis(2-hy-droxypropyl)amine XI (a potent pancreatic carcinogen in hamsters, the amino progenitor of which is used in many of the same applications as diethanolamine) (16), and the N-nitroso derivatives of the common drugs ephedrine XII (17) and ethambutol XIII (18), both of which have been shown to be carcinogenic. 

B. P. Chattopadhyay, J. Chattopadhyay, and P. C. Bose, Application of high pressure liquid chromatography for simultaneous estimation of aminophylline, codeine, ephedrine, and diphenhydramine in cough syrup, Indian Drugs, 22 154 (1984). 

As an example of a potential limitation, the drugs listed in Figure 1 have rather low molecular weights and relatively similar in molecular size. However, their skin permeation rates vary as much as 100 folds (2 mcg/cm /hr for fentanyl vs. 200 mcg/cm /hr for ephedrine). This difference in skin permeability will be reflected in the size of TDD system required to deliver the effective daily dose (Table I). A TDD system having a drug-releasing surface area of 90 cm is expected to be required for the delivery of diethylcarbamazine at a daily dose of 215 mg/day. From the standpoint of practical applications, a TDD system of this size would not be neither desirable nor economical. 

However signs do change with the "handedness" of the natural isomer so a higher level of distinction is achieved using CD or polarimetric detection. An enormous advantage is derived from the fact that achiral excipients, such as lidocaine, procaine, and benzocaine, often deliberately added to illicit drug preparations to complicate the chromatographic identifications of amphetamine and methamphetamine, present no interference problem whatsoever to CD detection. ORD detection was developed for the analysis of mixtures of pseudoephedrine and ephedrine [47], which because of the connection between anomalous ORD and CD, should be applicable to CD detection in the UV. 

Owing to the increase in attempted diversions of ephedra from licit trade involving States members of the European Union during 2006, the European Union decided in 2007 to treat ephedra as a natural product containing ephedrine that can be easily used or extracted by readily applicable and economically viable means, thus bringing it under the scope of article 12 of the 1988 Convention. 

Figure 2.10 Amphetamine 30, methamphetamine 31, and methylenedioxymethamphetamine 32 (MDMA, ecstasy, XTC) are lipophilic compounds with good oral bioavailability they easily cross the blood-brain barrier to exert central nervous system effects. Dopamine 33, norepinephrine (noradrenalin) 34, and epinephrine (adrenaline) 35 are polar phenethylamines they have poor oral efficacy and do not pass the blood-brain barrier, producing only peripheral effects after intravenous application. Ephedrine 36 has intermediate lipophilicity besides its peripheral effects it also acts as a central stimulant. Although L-dopa 37 is even more polar than dopamine 33, it is orally active and crosses the blood-brain barrier by active transport mediated by the amino acid transporter.

Leusen et al. studied the crystal packing of ephedrine with several phosphoric acid stereoisomers to verify whether a relationship between enthalpy of formation and separation of enantiomers via diastereomeric salt formation exists.They considered four different force fields and determined that the CHARMM program, as implemented in QUANTA, was the best for their application. Their decision was based mainly on the knowledge that non-bonded cutoff distances are larger in CHARMM. A larger cutoff distance is necessary to account for the interaction between different hydrophobic layers in the crystal (interlayer distances of 14—16 A). These authors were unable to quantitatively determine the validity of their hypothesis, although qualitative explanations were derived for their observations. 

Other Applications. Chiral oxazaborolidines derived from ephedrine have also been used in asymmetric hydroborations, and as reagents to determine the enantiomeric purity of secondary alcohols. Chiral l,3,2-oxazaborolidin-5-ones derived from amino acids have been used as asymmetric catalysts for the Diels-Alder reaction,and the aldol reaction. ... 

A 62-year-old man developed contact dermatitis after using phenylephrine eye-drops (Neosynerphin POS) (11). The inflammation affected both eyehds symmetrically and resolved rapidly on withdrawal of the eye-drops and application of topical glucocorticoids. Skintesting confirmed hypersensitivity to phenylephrine but no cross-sensitization to ephedrine or adrenahne. 

Bechgaard E, Bindseil E, Bagger M, Nielsen HW. Reversibility and clinical relevance of morphological changes after nasal application of ephedrine nasal drops 1%. Int Pharm 1997 152 67-73. 

The earliest example of the industrial application of a biotransformation for the synthesis of chiral pharmaceuticals was the production of (I )-phenylacetylcarbi-nol ((K)-PAC) by fermenting bakers yeast. This transformation is still in use to obtain this compound as a chiral intermediate for the synthesis of (-)-ephedrine (Scheme 4.1) [14]. 

Lefebvre RA, Surmont F, Bouckaert J, Moerman E. Urinary excretion of ephedrine after nasal application in healthy volunteers. J Pharm Pharmacol 1992 44 672-5. 

In an application of the chiral auxiliary technique, succindialdehyde has been transformed into mono-N-tosyloxazolidine 1.83 (n = 0, Y = CH=CHCOOH) derived from ephedrine. Treatment of 1.83 with KOC1 leads to an epoxyacid with high diastereoselectivity [1385], After nucleophilic ring opening of epoxide, the chiral auxiliary is recovered by treatment with ethanedithiol (Figure 7.35). Epoxidation of the (2, 47 )-pentane-2,4-diol monoketal of a prochiral quinone with tri-tylhydroperojdde has been performed with a moderate selectivity by Corey and Wu en route to a natural product (70%) [1386],... 

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