L-Epinephrine

Selective hydroxylation of some aromatic compounds can be achieved using HRP C in the presence of oxygen and dihydroxyfumaric acid (270). This process afforded l-DOPA from L-tyrosine, D-(-)-3,4-dihydroxy-phenylglycine from D-(—)-4-hydroxyphenylglycine, and L-epinephrine (adrenalin) from L-(-)-phenylephrine in yields of up to 70%. 

T. E. Peterson and D. Trowbridge, Quantitation of 1-epinephrine and determination of the d-/l-epinephrine enantiomer ratio in a pharmaceutical formulation by capillary electrophoresis, J. Chromatogr., 603 298 (1992). 

Thus, peroxidase is capable of catalyzing the synthesis of three important drugs, L-3,4-dihydroxyphenylalanine (XII) (Scheme VII), d-(-)-3,4-dihydroxyphenylglycine and L-epinephrine with yields up to 70 % [90]. 

Position Norepinephrine pg/mL (pmoi/L) Epinephrine pg/mL (pmol/L) Dopannine pg/mL (prhol/L)... 

Fig. 5-30. Separation of epinephrine, ephedrine, and opium alkaloids. - Separator column IonPac NS1 (10 pm) eluent 0.005 mol/L sodium octanesulfonate + 0.05 mol/L KH2P04 (pH 4.0) / acetonitrile (89 11 v/v) flow rate 1 mL/min detection UV (220 nm) injection volume 50 pL solute concentrations 10 mg/L epinephrine, 10 mg/L morphine sulfate, 20 mg/L ephedrine hydrochloride, and 20 mg/L codeine phosphate.

Figure 1-17. Hypothetical receptor interactions of epinephrine isomers. Left D-(-)-epinephrine. Right L-(+)-epinephrine.

Fig. 17.2 Interaction capacities of the natural R(-l-)-epinephrine with a model of its receptor (after References 20 and 21).

S(-l-) epinephrine, may establish only a two-point contact (b). The loss of the hydrogen bond interaction equals to approximately 3 kcal/mol, this isomer should therefore possess an approximately 100-fold lesser affinity. The experience confirms this estimate. If we consider less abstract models it becomes apparent that the less potent enantiomer also is able to develop three intermolecular bonds to the receptor, provided that it approaches the receptor in a different manner. However, the probabihty of this alternate binding mode to trigger the same biological response is close to null. 

The synthetic utility of this reaction was demonstrated by the oxidation of amino acids and -alcohols containing an electron-rich p-hydroxyphenyl moiety (Scheme 2.153). Thus, l-DOPA (3,4-dihydroxyphenyl alanine) used for the treatment of Parkinson s disease, o-3,4-dihydroxy-phenylglycine and L-epinephrine (adrenaline) were synthesized from their p-monohydroxy precursors without race-mization in good yield. 

Type II pneumocytes isolated from the lungs of rnide rats by treatment with elastase, discontinuous density centrifugation, and adherence in primary culture, after P-adrenergic stimulation (10/iM l-epinephrine, L-isoprenaline, OL-terbutaline, respectively) released significantly increased quantities of [ Cldisaturated phosphatidylcholine, the major component of surface-active material (Dobbs and Mason 1979). 

Papavasiliou and colleagues demonstrated an intracellular increase in the concentration of manganese in liver tissue after the administrations of DA, L-epinephrine, or DL-isoproterenol. It was also observed that this effect was mediated through an intracellular increase in cyclic 3, 5 -adenosine monophosphate. Although the importance of these studies in relation to manganese encephalopathy could not be evaluated, it became clear that a correlation existed between manganese metabolism and biogenic amines. 

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