Biocatalytic Oxidation of 2-Methylquinoxaline to 2-Quinoxalinecarboxylic Acid

A microbial process using the fungus Absidia repens ATCC 14849 is described for the oxidation of 2-methylquinoxaline to 2-quinoxalinecarboxylic acid. A campaign consisting of three 14000-L runs produced 20.5 kg of the acid with a 28% overall yield. The bioconversion gave a lower yield compared with a three step chemical synthesis (35%), but was carried out in one pot, and avoided safety issues with a di-N-oxide intermediate. Although successfully scaled to produce kilograms of 2-quinoxalinecarboxylic acid for synthesis of a drug candidate, the A. repens bioconversion is unsuitable for further scale-up due to low product concentration (∼1 g/L). A second microbial process using Pseudomonas putida ATCC 33015 is also described for the oxidation of 2-methylquinoxaline. The P. putida bioconversion gave an 86% in situ yield at 8-L scale and yielded a product concentration approximately 10-fold greater than that of the A. repens bioconversion.