Methylamine Epinephrine

The original commercial source of E was extraction from bovine adrenal glands (5). This was replaced by a synthetic route for E and NE (Eig. 1) similar to the original pubHshed route of synthesis (6). Eriedel-Crafts acylation of catechol [120-80-9] with chloroacetyl chloride yields chloroacetocatechol [99-40-1]. Displacement of the chlorine by methylamine yields the methylamine derivative, adrenalone [99-45-6] which on catalytic reduction yields (+)-epinephrine [329-65-7]. Substitution of ammonia for methylamine in the sequence yields the amino derivative noradrenalone [499-61-6] which on reduction yields (+)-norepinephrine [138-65-8]. The racemic compounds were resolved with (+)-tartaric acid to give the physiologically active (—)-enantiomers. The commercial synthesis of E and related compounds has been reviewed (27). The synthetic route for L-3,4-dihydroxyphenylalanine [59-92-7] (l-DOPA) has been described (28). 

The chemistry of most of the drugs in this family is quite simple, accounting in part for the very large number of analogues which have been made. The foundation for the chemistry in this series was laid long ago by Stolz in his classic synthesis of the ophthalmic agent adrenal one (3) in which he reacted catechol with chloroacetyl chloride and then displaced the reactive chlorine atom with methylamine to complete the synthesis. Borohydride reduction would have given epinephrine (adrenaline). 

Arterenol d-Arterenol d-Epinephrine Amylamine Phenethylamine Methylamine Ethylamine Choline Ethanolamine 0-Hydroxy propylamine 0-Aminopropionic acid 7-Aminobutyric acid Y-Amino-0-hydroxybutyric acid 0-Methylbutylamine Taurine... 

One monoamine oxidase has been found soluble in nature, and has been purified. This is the enzyme of blood serum, which has been purified 200-fold from steer plasma. The specificity of the serum enzyme is more restricted than those of the hver enzymes tryptamine and epinephrine are not oxidized rapidly, if at all, although phenylethylamine is a substrate. The polyamines spermine and spermidine are among the best substrates, and decamethylenediamine, but not shorter diamines, is also attacked. Aromatic substitutions on methylamine form substrates that permit spectrophotometric assays. Benzylamine and furfurylamine, for example, which do not absorb fight in the region used, are converted to benzaldehyde and furfuraldehyde, respectively these products have absorption maxima near 250 mja and 275 m/ . 

Secondary methylamines of the type R—CH2—NHCH3, including epinephrine, are oxidized to form methylamine in place of ammonia tertiary amines, RCH2—N(CH3)2, such as hordenine, react more slowly to form dimethylamine. 

---