5-hydroxypyrazine-2-carboxylic acid

Quantification. Gas Chromatography-Mass Spectrometry. In serum or urine pyrazinamide, pyrazine-2-carboxylic acid and 5-hydroxypyrazine-2-carboxylic acid, sensitivity 10 ng/ml for pyrazinamide—J. Koboz et al., J. Chromat., 1978,147, 337-347. 

Disposition in the Body. Well absorbed after oral administration. Metabolised by hydrolysis to pyrazine-2-carboxylic acid and subsequent hydroxylation to 5-hydroxypyrazine-2-carboxylic acid. In 24 hours, about 30 to 40% of a dose is excreted in the urine as pyrazine-2-carboxylic acid and less than 4% as unchanged drug the 5-hydroxy metabolite is also excreted in the urine. 

After an oral dose of 3 g to one subject, a peak serum concentration of 134 pg/ml was attained in 1 hour the serum concentration of pyrazine-2-carboxylic acid was 20 to 30 pg/ml after the first hour and the concentration of 5-hydroxypyrazine-2-carboxylic acid ranged between 3 and 8 M-g/ml over a period of 12 hours (J. Roboz et al., ibid.). 

Figure 19-35. Biocatalytical synthesis of 5-hydroxypyrazine-2-carboxylic acid (Lonza).

Hydroxypyrazine-2-carboxylic acid (Fig. 19-35) is a versatile building block in the synthesis of new antituberculous agents, e.g. 5-chloro-pyrazine-2-carboxylic acid esters. The regioselective hydroxylation of pyrazine-2-carboxylic acid is catalyzed by a hydroxylase (E2, E. C. 1.5.1.13). This second enzyme is also in the applied suspended whole cells from Agrobacterium sp. The biomass is separated by ultrafiltration (cutoff 10 kDa) after the biotransformation. 5-Hydroxypyrazine-2-carboxylic acid is precipitated from the permeate by acidification with sulfuric acid to pH 2.5. 

Hydroxypyrazine-2-carboxylic acid [121] Nitrilase and dehydrogenase Agrobacterium sp. 

Figure 11.8 Reaction sequence analogies of 3-cyanopyridine 1 degradation and 2-cyanopyrazine 4 transformation (through nicotinic acid 2 and 6-hydroxy-nicotinic acid 3 or pyrazinecarboxylic acid 5 and 5-hydroxypyrazine-2-carboxylic acid 6 respectively). Figure reproduced from [49] with kind permission from Springer Science and Business media.

Wieser, M., Heinzmann, K., and Kiener, A. (1997) Bioconversion of 2-cyanopyrazine to 5-hydroxypyrazine-2-carboxylic acid with Agrobacterium sp. DSM 6336. Appl. Microbiol. Biotechnol., 48, 174-176. 

Several reactions of pyrazinecarboxylic esters have been discussed already reduction to N-alkylpiperazines (Section 3.2.2.2), reduction to extranuclear hydroxypyrazines (Section 5.2.1), and hydrolysis to pyrazinecarboxylic acids (Section 8.1.1). Other reactions to be expected of carboxylic or carboximidic esters are typi-hed in the following class lied examples ... 

---