Catechol, /.-dopa synthesis from

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). 

In fluorine-18 chemistry some enzymatic transformations of compounds already labelled with fluorine-18 have been reported the synthesis of 6-[ F] fluoro-L-DOPA from 4-[ F]catechol by jS-tyrosinase [241], the separation of racemic mixtures of p F]fluoroaromatic amino acids by L-amino acylase [242] and the preparation of the coenzyme uridine diphospho-2-deoxy-2-p F]fluoro-a-o-glucose from [ F]FDG-1-phosphate by UDP-glucose pyrophosphorylase [243]. In living nature compounds exhibiting a carbon-fluorine bond are very rare. 

Tyrosine phenol lyase (p-tyrosinase) has been shown to catalyze the efficient synthesis of the L-amino acids L-tyrosine and L-dopa from pyruvate, ammonia and phenol, or catechol, respectively (87-89). 

A further industrially important lyase for the production of L-amino acids is the tyrosine phenol lyase [39]. This biocatalyst is used by Ajinomoto in the production of the pharmaceutically important L-3,4-dihydroxyphenylalanine (L-dopa), 32, which is applied in the treatment of Parkinson s disease. The reaction concept is based on a one-pot three-component synthesis starting from catechol, 30, pyruvic acid, 31, and ammonia in the presence of suspended whole cells (strain Erwinia herbicola) containing the tyrosine phenol lyase biocatalyst (Fig. 16). A key feature of this process is the high volumetric productivity of 110 g/L of the desired L-dopa product. Notably, this reaction runs with an annual capacity of 250 tons. 

The first and rate-limiting step in the synthesis of these neuroffansmitters from tyrosine is the hydroxylation of the tyrosine ring by tyrosine hydroxylase, a teffahy-drobiopterin (BH4)-requiring enzyme. The product formed is dihydroxyphenylala-nine or DOPA. The phenyl ring with two adjacent OH groups is a catechol, and hence dopamine, norepinephrine, and epinephrine are called catecholamines. 

Japanese workers have described a novel microbiological synthesis of L-tyrosine and L-dopa from sodium pyruvate, ammonia and phenol or catechol respectively, using cells of Erwinia herbicola. The reaction is catalysed by tyrosine phenol lyase and is the reverse of the normal a)3-elimination reaction catalysed by this enzyme. The L-tyrosine or L-dopa synthesised by this enzymatic method precipitates from the reaction media during incubation. The maximum amount of L-tyrosine synthesised by this method was 60.5 g per litre and of L-dopa 58.5 g per litre. The process is a variation on the analogous procedure reported by the same school which used d L-serine in place of sodium pyruvate. 

Although the data above established that NAcDEE could undergo an a,p-desaturation on the side chain following oxidation to the quinone, we felt it desirable to see whether further information could be gleaned about the mechanism and rate of synthesis, since we were interested in this reaction as a model for the reactivity of peptidyl DOPA. The chemistry of catechols and their quinones is notoriously complex, and it was not obvious that a realistic extrapolation from this low molecular... 

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