Alkaloids pseudoephedrine

OFFICIAL NAMES Ephedra, Ephedra sinica STREET NAMES Mahuang, ma huang, desert tea, Mormon tea, American ephedra, European ephedra, Pakistani ephedra, ephedrine, ephedrine alkaloids, pseudoephedrine DRUG CLASSIFICATIONS Not scheduled, dietary supplement... 

At one time, Coca-Cola actually contained a form of cocaine. These days, the primary stimulant in Coca-Cola and many other beverages is caffeine. Other stimulants are less obvious. Chocolate contains theobromine, a caffeinelike stimulant. Nondrowsy cold remedies contain pseudoephedrine, a relative of ephedra, another plant-alkaloid stimulant. 

Cervinka and co-workers have extensively investigated the asymmetric reduction of prochiral ketones with LAH modified with alkaloids and related amino alcohols. Most of this work has been reviewed in detail by Morrison and Mosher (1) and will not be discussed extensively here. Modification of LAH was effected with (-)-quinine (65), (- )-cinchonidine (66), (- )-ephedrine (67), (-)-A-ethyl-ephedrine (68), (-)- l-phenyl-2-dimethylaminoethanol (69), (+ )-quinidine (70), (+ )-cinchonine (71), and (+ )-pseudoephedrine (72). 

In the alkaloid synthesis, L-phenylalanine (Figure 30) provides to alkaloid the phenyl or phenylpropyl nucleus. These kinds of nuclei occur in cathionine, cathine, ephedrine, pseudoephedrine and norpseudoephedrine. Such alkaloids are found especially in many species of Ephedra. Natural alkaloid molecules from these plants have similar properties to synthetic compounds used as narcotics (e.g., amphetamine). 

Pseudoephedrine Alkaloid Clears nasal congestion Ephedra sinica... 

Ephedrine has not been extensively studied in humans despite its long history of use. Its ability to activate 3 receptors probably accounted for its earlier use in asthma. Because it gains access to the central nervous system, it is a mild stimulant. Ingestion of ephedrine alkaloids contained in ma huang has raised important safety concerns. Pseudoephedrine, one of four ephedrine enantiomers, has been available over the counter as a component of many decongestant mixtures. However, the use of pseudoephedrine as a precursor in the illicit manufacture of methamphetamine has led to restrictions on its sale. 

N.A. Alkaloids, ephedrine, 1-ephedrine, d-pseudoephedrine.106129511 Treat fevers, relieve kidney pain, asthma, nose and lung congestions, hay fever, and as a hypertensive aid. 

The thought that transmethylation of noradrenaline may be an initial step in its deactivation in the body makes one wonder whether further transmethylation of adrenaline is also not a common biological process. As a result of studies of the various alkaloids of plants of the Ephedra species, it was noted that not only Z-ephedrine and its stereoisomer d-pseudoephedrine are present but also that -norephedrine, d-norpseudoephedrine, l-methylephedrine, and d-methylpseudoephedrine (8) are present. The quaternary tri-methylammonium compounds corresponding to these were not reported but very... 

The alkaloids dealt with in this section of the chapter are hyoscyamine (1), scopolamine (2), methylephedrine (3), norephedrine (4), ephedrine (5), pseudoephedrine (6), and cephalotaxine (7). 

Opium alkaloids such as codeine, thebaine, papaverine, and noscapine exhibit high solubility (0.09-0.9 mg/g) in supercritical fluids including CO N,0, CHF, [37]. However, in spite of their high solubilities, they were not extracted from plant material by pure CO, to the degree expected [29], possibly because these alkaloids exist as their salt forms in plant tissue. In this chapter, the examples that show the difference of the solubilities between alkaloidal free bases and salts are presented. For this comparison, the solubilities of the free bases of hyoscyamine (1), scopolamine (2), pseudoephedrine (6) were measured and compared with those of their hydrochloride salts (Figures 3 and 4). 

Although there were some differences on the effects of temperature and pressure according to each particular compound, the free bases of hyoscyamine (1), scopolamine (2), and pseudoephedrine (6) were all found to be highly soluble in supercritical CO,. However, the hydrochloride salts of these compounds were scarcely extracted by pure CO, under any conditions employed. These results were consistent with preliminary evidence indicating that these alkaloids are not extracted from plant materials by pure CO,. This means that the alkaloids in living cells in the plant are not in the form of their free bases but rather as water-soluble salts in the cell vacuole [40]. Therefore, it was necessary to develop a procedure to enhance the solubilities of alkaloidal salts in CO,. 

Various species of Ephedra grow in different parts of the world. It is believed that the Chinese species contain the official levorotatory ephedrine, whereas the same species and other varieties from Europe yield only dextrorotatory pseudoephedrine. East Indian species range from rich to none. Ephedrine exists in the seed of another, totally unrelated Indian plant, Sida cordifolia, which was also used in folk medicine. Ma huang also contains another alkaloid, ephedine, which lowers blood pressure and has other complex actions. 

The oriental crude drug Ma Huang or Mao, prepared from certain species of the genus Ephedra, contains ephedrine, pseudoephedrine, and homologous compounds (2). Although alkaloids of the ephedrine type occur in several Ephedra species, only a few other plant sources are known (Table IV and V). 

The six optically active alkaloids ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine, and the N-methylated N-methylephedrine and N-methylpseudoephedrine are described in detail in Reti s review (2). Two new alkaloids of related structure have since been identified in Ephedra species, namely, (9-benzoylpseudoephedrine (271) and the oxazolidine derivative ephe-droxane (272). The 4-quinolone derivative ephedralone, recently isolated from Ephedra alata (273), may be of similar biogenetic origin as the ephedrines. Ephedra species also contain macrocyclic alkaloids of more complex structure (275). The two major Ephedra alkaloids (—)-ephedrine and (+)-pseudoephedrine are diastereomers. (—)-Ephedrine has the erythro and (+)-pseudoephedrine has the threo configuration. 

Key to alkaloids Dop, dopamine Epi, epinephrine Eph, ephedrine i/iEph, pseudoephedrine Homova, homoveratrylamine Hord, hordenine Macr, macromerine Mesc, mescaline Oct, octopa-mine Phe, phenethylamine Synephr, synephrine Tyr, tyramine. 

The isoquinoline alkaloids are the second largest group of alkaloids, numbering about 6000, and can be viewed as five subgroups—the simple tetrahydroisoquinolines, the benzylisoquinolines, the phenethylisoquinolines, the Amaryllidaceae alkaloids, and the monoterpene isoquinolines. In addition, there are a number of simple phenethylamine derivatives, including ephedrine (originally from Ephedra species, but now synthesized) and pseudoephedrine, used for asthma and nasal... 

The medicinal use of Ephedra sinica in China dates from 2800bc. Ma Eluang (the stem and branch) was used primarily in the treatment of common cold, asthma, hay fever, bronchitis, edema, arthritis, fever, hypotension, and urticaria. Ephedra has been used to treat bronchoconstriction for centuries, because of its activity at /li-adrenergic receptors. It contains pseudoephedrine, ephedrine, and other similar alkaloids. These are sympathomimetics that either directly or indirectly stimulate a- and jS-adrenergic receptors. It has become less extensively used with the advent of more selective agonists. 

As with other sympathomimetic agents, theoretical drug interactions with ephedra alkaloids are possible. Despite this potential, only a handful of adverse drug interactions have been reported. This is especially pertinent when considering the extensive use of both ephedra-containing supplements and ephedrine- or pseudoephedrine-containing OTC products. The most notable interaction exists between nonselective monoamine oxidase inhibitors and ephedra- or ephedrine-containing products. 

Ephedrine alkaloids include ephedrine, pseudoephedrine, and norephedrine (phenylpropanolamine, PPA). 

Since there are two possible configurations for an asymmetrically substituted carbon atom, a structure containing n such centres will, in theory, possess 2 stereoisomers. The actual number of stereoisomers that exist may be less than this due to steric effects. Compounds that have the same stereochemistry at one chiral centre but different stereochemistry at the others are known as diastereoisomers (diastereomers) a good example is given by the alkaloids ephedrine and pseudoephedrine. Ephedrine (the (1R, 2S) diastereoisomer) is a natural product isolated from Ephedra (the Ma Huang plant) and known to Chinese medicine for over 3000 years. It was used in the last century for the treatment of asthma. Pseudoephedrine (the (IS, 2S) diastereoisomer) is a decongestant and a constituent of several over-the-counter cold and flu remedies (Figure 4.12). 

Ephedrine and ist isomer pseudoephedrine are alkaloids in Ephedra species. Brochmann-Hans-sen and Baerheim Svendsen reported the first gas chromatographic separation of these two alkaloids in a study on the separation and identification of 11 sympathomimetic amines on a 1.15 % SE-30 packed column at 104°C. However, ephedrine and pseudoephedrine could not be separated as such, but were separated as their oxazolidine derivatives after treatment with acetone. A typical chromatogram is given in Tale 13.1. 

Yamasaki et al. applied gas chromatography to the separation and quantitative analysis of the alkaloids in some Ephedra species collected around the Himalayas. A satisfactory separation of the alkaloids and quantitative determination of L-ephedrine and D-pseudoephedrine was achieved using oxazolidine formation with acetone. ... 

Figure 5 High-performance strong cation-exchange chromatography of ephedrine alkaloids and synephrine in dietary supplements. UV and fluorescence chromatograms of (A) standard solution ( 3 ng per component, except 1.6 tg of component 1), (B) Xenadrine RFA-1, (C) Xetalean, and (D) Ultra Diet Pep. Analytes 1, ( )-synephrine 2, (-)-norephedrine 3, (+)-norpseudoephedrine-HCI 4, (-)-ephedrine-HCI 5, (+)-pseudoephedrine 6, (-)-A/-methylephedrine 7, (+)-N-methylpseudoephedrine. Reproduced from R. A. Niemann M. L. Gay, J. Agric. Food Chem. 2003, 51, 5630-5638.

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