Ephedrine isomers

Bicker and Fischer incubated ephedrine isomer 127 with a rat liver homogenate to which ATP and sulfate were added [191]. Formation of aziridine 128, requiring... 

From calculations of the preferred conformation of the ephedrine and pseudo ephedrine molecules the topography of the adrenergic receptor as a flat surface has been deduced (26). This view, however, does not explain the decisive effect of the additional methyl group its relative position should not influence the interaction with the proposed receptor to a large extent (Fig. 7a). However, as the differences in activities are especially high for the ephedrine and pseudo ephedrine isomers, we believe that the receptor must have an intercalated structure similar as projected for the "binding sites" of the silicones (Fig. 7b). ... 

The pharmacokinetic and toxicokinetic behavior of any isomer cannot be used to predict that of any other ephedrine isomer. The (+) isomer of meth-amphetamine, for example, is a potent CNS stimulant, but the (-)-isomer is merely a decongestant. There is a tendency in the literature to lump together all ephedrine alkaloids and use the term class effect to assume that all the different drugs in that class exert the same effects on the same biological targets. In fact, some of the drugs in the class will be similar in some regards and different in others. 

Vansal SS, Feller DR. Direct effects of ephedrine isomers on human beta-adrenergic receptor subtypes. Biochem Pharmacol 1999 58(5) 807—810. 

Kier, L. B. The preferred conformations of ephedrine isomers and the nature of the alpha adrenergic receptor. J. Pharmacol. Exp. Then 1968,164, 75-81. 

Portoghese, P. S. Stereochemical studies on medicinal agents. IV Conformational analysis of ephedrine isomers and related compounds. J. Med. Chem. 1967,10, 1057-1063. 

The separation of the pseudoephedrine and ephedrine isomers was carried out using 3-cyclodextrins in the mobile phase. The separation, shown in figure 13.7, was carried out on a capillary 72 cm x 50 p,m ID. and the solutes were detected by UV adsorption at 214 nm. The mobile phase chiral additive was the sulfobutylether derivative of P-cyclodextrin. 

Tye A, Baldesbeiger R, Lapidus JB, Patil PN (1967) Steric aspects of adrenergic drugs. VI. Beta adrenergic effects of ephedrine isomers. J Pharmacol Exp Ther 157 356-362 Ul chenko NT, Glushenkova A1 (2(X)1) Oxygenated fatty acids from neutral lipids of Artemisia leucodes seeds. Chem Nat Compd 37(5) 406-408... 

Abdallah, A. H., 1968, Anorectic activity of ephedrine isomers. Life Set 1 665,... 

Vansal, S.S. and Feller, D.R., Direct effeets of ephedrine isomers on human 8-adrenergie receptor subtypes, Biochem. Pharmacol., 58, 807, 1999. 

Pseudoephedrine is an isomer of ephedrine in which the hydroxyl group is on the other side of the molecule. 

Treatment of (-)-ephedrine (42) with methylthiophosphonic dichloride afforded a mixture of the isomeric 2-methyl-l,3,2 oxazaphospholidine-2-thiones 120a,b, from which the pure isomers could be separated in approximately equal quantities by chromatography over silica (Scheme 34) [32],... 

Now the other three of the possible four stereoisomers are the (15,25), (l/f,2/f), and (15,2/f) versions. These are also shown, and mirror image relationships are emphasized. The (15,2/f) isomer is the mirror image of (—)-ephedrine, which has the (l/f,25) configuration. Therefore, it is the enantiomer of (—)-ephedrine, and can be designated (+)-ephedrine. Note that the enantiomeric form has the opposite configuration at both chiral centres. 

Now for a rather unexpected twist. We have seen that if there are n chiral centres there should be 2" configurational isomers, and we have considered each of these for n = 2 (e.g. ephedrine, pseudoephedrine). It transpires that if the groups around chiral centres are the same, then the number of stereoisomers is less than 2". Thus, when n = 2, there are only three stereoisomers, not four. As one of the simplest examples, let us consider in detail tartaric acid, a component of grape juice and many other fruits. This fits the requirement, since each of the two chiral centres has the same substituents. 

We can easily draw the four predicted isomers, as we did for the ephedrine-pseudoephedrine group, and two of these represent the enantiomeric pair of (—)-tartaric acid and (+)-tartaric acid. Now let us consider the other pair of isomers, and we shall see the consequences of... 

Rh-H / -elimination step in step E gives the vinyl-borane which then dissociates to generate the first intermediate. This cycle explains the production of equimolar quantities of alkane and -vinylborane with unreactive R2BH derived from ephedrines with catecholborane there is an additional shunt pathway — step C in competition with step E leading to the primary regio-isomer of alkylborane. 

Ephedrine Ephedrine, L-erythro-l-phenyl-2-methylaminopropanol-l (11.3.4), is synthesized from benzaldehyde in a few different ways. According to the first, benzaldehyde is condensed with nitroethane, giving 2-methyl-2-nitro-l-phenylethanol (11.3.2), which is reduced to 2-methyl-2-amino-l-phenylethanol (11.3.3). The necessary L-isomer is isolated from the mixture of isomers by crystallization. Methylation of this gives ephedrine (11.3.4) [52,53]. 

Such observations are naturally simpler in cyclic compounds, such as in ephedrine derivatives (65) when 37(PNCH) are 2-3 and TO Hz depending upon the isomer. (1989 109> This effect is even more pronounced in cyclic Pv compounds(1968,76) such as 66 in which the two 37(PNCH) values are clearly distinguished and have opposite signs ( + 1T5 and -0-31 Hz). 

The (2 S)-diastcrcomer is the major isomer starting material is derived from ( + )-ephedrine. 

It is a synthetic compound with structural similarity to ephedrine and is available in racemic and dextro isomers. It increases the systolic and diastolic blood pressure. Amphetamine is a potent CNS stimulant and causes alertness, insomnia, increased concentration, euphoria or dysphoria and increased work capacity. Amphetamine produces wakefulness and improved physical performance. It contracts the sphincter of the bladder and relaxes the bronchial smooth muscle in large doses. Amphetamines are drugs of abuse and can produce behavioural abnormalities and can precipitate psychosis. It can produce psychological but no physical dependence. 

Chen, . K. 1929. Relationship between the pharmacological action and the chemical constitution and configuration of the optical isomers of ephedrine and related compounds. J. Pharmacol. 36 363-400. 

Notice that ephedrine has two chiral carbons. This would give rise to four possible optical isomers- two pairs of enantiomers and four sets of diastereomers. One of the diastereomers is called pseudoephedrine. 

The mixture of isomers 35 (1.69 g, 7.43 mmol) was treated with (lS,2/ )-(+)-ephedrine (1.22 g, 7.43 mmol) and crystallized (CH2C12). After extensive fractional crystallization of the salts[18l and regeneration of the acid, enantiomerically pure oxazolidinone was obtained yield 0.48 g (20% based on aldehyde 34). 

EXTENSIONS AND COMMENT ARY Here is another example of the presentation of a compound for which there has not yet been an effective level determined. Why For a very good reason. This is an example of a whole class of compounds that I have called the pseudos, or the -compounds. Pseudo- as a prefix in the literary world generally stands for false. A pseudopod is a thing that looks like a foot, but isn t one. A pseudonym is a fictitious name. But in chemistry, it has quite a different meaning. If something has a common name, and there is a second form (or isomer, or shape, or orientation) that is possible and it doesn t have a common name, it can be given the name of the first form with a pseudo- attached. Ephedrine is the erythro-isomer of N-methyl-13-hydroxyamphetamine. There is a second stereoisomer, the threo- isomer, but it has no trivial name. So it is called pseudoephedrine, or the Sudafed of sinus decongestant fame. 

This alkaloid was first isolated from Ephedra equisetina, a plant (ma huang) that has been used as medicine by the Chinese since antiquity. Most of the present supply is probably synthetic. Its chemical structure is closely related to epinephrine and tyramine, and differs from epinephrine chiefly by the absence of the two phenolic hydroxyls. Its effects on the circulation, intestines, bronchi, iris, etc., are superficially similar to those of epinephrine. It requires that larger doses be given but they are more lasting, due probably to ephedrine s much greater stability and resistance to oxidation. The effects can be produced by oral administration. Unlike epinephrine, it is not sensitized by cocaine or by denervation. From this, it has been argued that its point of attack is not sympathomimetic but muscular. It also stimulates the CNS. A number of isomers with similar actions are known. Ephedrine is used therapeutically in hay fever and asthma, in which it is less... 

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