S -Ephedrine

Nagai s ephedrine was obtained from Ma-Huang and the same alkaloid, together with its stereoisomeride pseudoephednne ( -ephedrine), was isolated by Merck from the European species, E. helvetica C. A. Meyer. From commercial Ma-Huang Smith prepared two additional bases, 1-W-methylephedrine and nnr-d- -ephedrine. Nagai and Kanao added two more, viz., d-W-methyl- -ephedrine and Z-norephedrine, and... 

A further, indirect indication of methamphetamine production can be derived from the geographical location of ephedrine and pseudo-ephedrine seizures. The largest such seizures in Asia over the 2004-2005 period were reported from China (which is also one of the main licit producers of ephedrine and pseudo-ephedrine), followed by the Philippines, Myanmar, Indonesia and India (another major licit producer of ephedrine and pseudo-ephedrine), and at far lower levels, Hong Kong SAR of China and Thailand. Taken together, the Asian countries accounted for 89 per cent of the world s ephedrine and pseudo-ephedrine seizures in 2005.20... 

Ramamurthy et al. have examined enantioselective and diastereoselective ODPM rearrangements of cyclohexadienone and naphthalenone derivatives within MY zeolites, where M is an alkali ion [38, 39]. For example, in Scheme 4.27, in NaY in the presence of several chiral inductors such as ephedrine, pseudoephedrine, and camphorquinone-3-oxime, an enantioselective ODPM rearrangement of 65 and 66 took place to afford 68 in 30% ee yield. In the frame of the chiral auxiliary approach, the compound 67 linked to (S)-ephedrine was irradiated within NaY to give 68 in moderate diastereoselective excess (de) (59%). Interestingly, the reaction media of KY, RbY, and CsY reverse the diastereoselectivities. The cation-dependent diastereo-meric switch has been discussed with respect to the N- or O-functional group in 67 [39]. Recently, Arumugan reported that the irradiation of naphthalenones 65 linked chiral auxiliaries (R3 = COO(—)-Ment or (S)-NHCH(Me)Ph) in Li+ or Na + Nafion resulted in chiral products ( 14% de) [40],... 

SYNS BENZENEMETHANOL, 0-(l-(METHYLAXnNO)ETHYL)-, HYDROCHLORIDE, (R-(R, S ))- EPHEDRINE HYDROCHLORIDE 1-EPHEDRINE, HYDROCHLORIDE N-METHYL-P-OXY-P-PHENYLISOPROPYLAMINHYDROCHLORID... 

As these alkaloids are not only used in chemistry as chiral auxiliaries, starting materials, and catalysts, but also in medicine, so technical syntheses have been developed and all of these compounds are commercially available. The standard materials ( )-(l/ ,2,S )-ephedrine [(-)-3) and ( —)-(lff,25,)-norephedrine [(-)- ] are produced in a technical process on multikilogram scale by reductive amination (with methylamine or ammonia, respectively) of (—)-(f )-l -hydroxy- Tphenyl-2-acetone with a platinum catalyst1. The ketone is in turn obtained by a biotechnological procedure from cultures of selected yeast strains (Saccharomyces sp.)2. 

A new strategy for optically active chiral polymers was envisaged and based on a Suzuki coupling polymerisation of (li ,2 S)-ephedrine unit-bearing monomer with rigid linkers [129], The Suzuki coupling of ephedrine-derived dibromide 163 (which was prepared in four steps from (17 ,25)-ephedrine) with the diboronic acid 164 in presence of Pd(PPh3)4 afforded chiral... 

Progress has been made toward enantioselective and highly regioselective Michael type alkylations of 2-cyclohexen-l -one using alkylcuprates with chiral auxiliary ligands, e. g., anions of either enantiomer of N-[2-(dimethylamino)ethyl]ephedrine (E. J. Corey, 1986), of (S)-2-(methoxymethyl)pyrrolidine (from L-proline R. K. EHeter, 1987) or of chiramt (= (R,R)-N-(l-phenylethyl)-7-[(l-phenylethyl)iinino]-l,3,5-cycloheptatrien-l-amine, a chiral aminotro-ponimine G. M. Villacorta, 1988). Enantioselectivities of up to 95% have been reported. 

The world war made all these sources of supply difficult of access and stimulated interest in the possibilities of local production. Examination of a number of American species of ephedra had already shown them to be devoid of alkaloids, except for the S. American species E. andina, in which Chavezt found ephedrine, and in the United States attention has been given to the experimental cultivation of imported species, notably E. sinica and E. gerardiana a Moroccan type, E. alenda, was found to contain only ). In Australia experimental cultivation of the Indian species E. gerardiana, E. intermedia and E. nebrodensis has been tried and preliminary yields of 1-35, 1-OS and 0-98 per cent, of total alkaloids respectively have been recorded. In Russia, E. equisetina and E. intermedia are available and are considered to be worth exploitation. In Italy various local species have been found to contain mainly i -ephedrine and that in small amount, but better results are recorded for two species already referred to and which are available in Sardinia, viz. E. vulgaris Rich and E. nebrodensis. ... 

Ephedrine also oeeurs in the leaves of the yew tree [Taxus baccata) and in Sida rhombifolia Linn, whilst Stockman s cathine from Catha edulis Forsk has been shown by Wolfes to be d-nor- -ephedrine. Ghosh, Chopra and Dutt state that the bark of Moringa pterygosperma Gaertn. contains two alkaloids similar to ephedrine in pharmacological action. The more active of the two, moringinine, is amorphous the other is a liquid but jdelds a crystalline hydrochloride, C,H. HCl, m.p. 254-4°, + 1-8°, a picrate, m.p. 195°, and an aurichloride, m.p. 170-8°. 

The oxazaborolidines are easily prepared by heating ephedrine with borane dimethyl sulfide or the appropriate boronate ester. The aluminum reagent C is obtained by mixing ephedrine and trimethylaluminum. Borolidinc A is superior to its methyl derivative B and to the aluminum analog C. The diastereomeric borolidine obtained from borane and (S,S)-pseu-doephedrine failed to show any cnantioselectivity25. A variety of aromatic aldehydes can be enantioselectively alkylated in the presence of A, however, with heptanal the enantioselectivity is poor25. 

Additive sympathomimetic effects may develop when decongestants are administered with other sympathomimetic drug s (see Chap. 22). Use of the nasal decongestants with the MAOIs may cause hypertensive crisis. Use of a decongestant with beta-adrenergic blocking dragp may cause hypertension or bradycardia. When ephedrine is administered with theophylline, the patient is at increased risk for theophylline toxicity. 

Der Komplex aus Lithiumalanat, (-)- bzw. (+)-N-Methyl-ephedrin und 3,5-Dime-thyl-phenol reduziert unverzweigte Alkyl-aryl-ketone in Ausbeuten iiber 90% und optischen Ausbeuten von 62 bis 80% zu den (+)-(R)- bzw. (-) -(S)-1 -Phenyl-alka-nolen . 

Kcurentjes et al. (1996) have also reported the separation of racemic mixtures. Two liquids are made oppositely chiral by the addition of R- or S-enantiomers of a chiral selector, respectively. These liquids are miscible, but are kept separated by a non-miscible liquid contained in a porous membrane. These authors have used different types of hollow-fibre modules and optimization of shell-side flow distribution was carried out. The liquid membrane should be permeable to the enantiomers to be separated but non-permeable to the chiral selector molecules. Separation of racemic mixtures like norephedrine, ephedrine, phenyl glycine, salbutanol, etc. was attempted and both enantiomers of 99.3 to 99.8% purity were realized. 

Scheme 3.4 Ephedrine-derived S/N ligands for addition of ZnEt2 to benzaldehyde.

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