Fluorophenylpyruvic acid

Here, we describe, as a representative example, an efficient chemical synthesis of 4-fluorophenylpyruvic acid (Procedure 1, Section 10.5.1) followed by its biocatalytic conversion to L-4-fluorophenylalanine catalysed by the N145V mutant of PheDH (Procedure 2, Section 10.5.2). 

The reaction was allowed to cool to room temperature and HCl 12 m was added dropwise to generate the free acid. The 4-fluorophenylpyruvic acid was extracted with EtOAc and the organic layer was dried with MgS04 (which was then removed by passing through filter paper) and evaporated in vacuo. 4-Fluorophenylpyruvic acid was obtained as a yellow solid (0.7 g, 73 %). 

The migration of alkyl substituents during the hydroxylation of 4-hydroxyphenylpyruvic acid (25) and 4-fluorophenylpyruvic acid (27) (Figure 8) provides another example of the NIH Shift and was formerly thought to be a unique phenomenon. It is in a sense atypical since a decarboxylation accompanies the hydroxylation and side chain migration. 

The effects of this inhibitor on the metabolism of A. fumigatus were very different from those of the other compounds used, since formation of all the characteristic acetate-derived phenols was strongly suppressed (Packter and Collins, 1974). Treatment of cultures gave a completely altered pattern and led unexpectedly to the secretion of atypical shikimic acid-derived phenols, including 2,3-dihydroxybenzoic acid, 4-hydroxyphenylpyruvic acid, and 4-hydroxybenzyl cyanide. In addition, the inhibitor was metabolized directly by transamination to fluorophenylpyruvic acid. 

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