Phenylacetic acid, 4-hydroxy-3-methoxy

Dopamine metabolism was covered in the discussion of general catecholamine biochemistry. Dopamine is stored in synaptic vesicles, and this storage can be manipulated. Although the reuptake of released DA is the major deactivating mechanism, MAO and COMT act enzymatically on DA in the same way as on NE. However, following the degradative pathway of NE, DA will finally be metabolized to homovanillic acid (3-methoxy-4-hydroxy-phenylacetic acid), since it lacks the P-hydroxyl group. 

In studies in man, less direct approaches are necessary and the concentrations of metabolites in CSF have been used to estimate central catecholamine turnover. Several GC-MS assays have been developed for the determination of homovanillic acid (HVA, 4-hydroxy-3-methoxy-phenylacetic acid), the major metabolite of dopamine [457,458,464,465]. 

A synthetic route to ( )-0,f>-dimethyltubocurarine iodide (CXXV), via the racemate of 0,0-dimethylbebeerine (CXXIII), was announced in 1959 by Tolkachev and his collaborators (94). It started by the condensation of 3-methoxy-4-hydroxyphenethylamine with 4-benzyloxy-phenylacetic acid to give the amide CXXVI. Reaction of the potassium salt of the latter with the methyl ester of 3-bromo-4-methoxyphenyl-acetic acid in the presence of copper powder gave compound CXXVII. This on condensation with 3-methoxy-4-hydroxy-5-bromophenethyl-amine afforded compound CXXVIII, which was methylated to CXXIX. The latter compound was cyclized with phosphorous oxychloride to the dihydroisoquinoline derivative CXXX. Debenzylation of CXXX followed by intramolecular Ullmann condensation yielded compound CXXXI. The latter was converted to racemic dimethylbebeerine (CXXIII) by reduction with zinc dust in acetic acid followed by methyla-tion. Finally, treatment of ( + )-CXXIII with methyl iodide furnished the dimethyl ether of ( + )-tubocurarine iodide, identified by comparison of its UV-spectrum with that of the dimethyl ether of natural tubo-curarine iodide and by melting-point determination of a mixture of the two specimens. 

For the determination of the absolute stereochemistry by NMR spectroscopy, Mosher derivatives are widely used [25]. This method is based on the formation of (R)/(S)-MTPA (a-methoxy-a-(trifluormethyl)phenylacetic acid) esters and comparison of the NMR data of both diastereomers. However, it is limited to compounds with amenable functional groups to be derivatized (typically hydroxy groups) and in some cases the conclusions from the NMR experiments are unsafe. 

Obtained by reaction of 3-hydroxy-4-methoxy-phenylacetic acid with pyrocatechol dimethyl ether in the presence of phosphoric acid [6272]. 

The methoxy substituent (14c) showed a much cleaner behavior, yielding only two products from the chromophore,p-methoxyacetophenone and the rearrangement product p-methoxyphenylacetic acid. The p-hydroxyphenacyl phosphate (33) gave the rearranged p-hydroxyphenylacetic acid when photolyzed in mixed aqueous organic solvents (Eq. (69.12)) in fact, of all of the groups examined, only p-hydroxy and p-methoxy produced any rearranged phenylacetic acids. 

Optical enantiomers of the methyl esters of monohydroxy fatty acids can be resolved by gas chromatography if they are first converted to the (-)-menthyl, D-phenylpropionyl or related derivatives [348,468] (reviewed briefly elsewhere [456,858]). Particularly good results were obtained with racemic methyl 2-hydroxy palmitate and stearate, after conversion to the (-)-a-methoxy-a-trifluoromethyl-phenylacetate derivatives, on a WCOT column coated with OV-1 as shown in Figure 5.17 [93] it is probable that the D-form elutes first. Some limited success has also been achieved in separating diastereoisomers of polyhydroxy fatty acids [988],... 

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