Synthesis of pyrazine via chemoselective reduction of β-keto-α-oximino ester using baker’s yeast

• Pyrazines were prepared from β-keto-α-oximino esters using baker’s yeast.
• Baker’s yeast reduced oxime selectively over ketone.
• β-Keto-α-amino ester might be a key intermediate toward pyrazines.
• β-Keto-α-oximino amide reacted with baker’s yeast to give pyrazines too.
• Pyrazines were prepared efficiently and eco-friendly by biocatalyzed reaction.

The synthesis of pyrazines by the baker’s yeast-mediated reaction of β-keto-α-oximino esters and amides is described. Baker’s yeast reduced oximes selectively over ketones of β-keto-α-oximino esters to give the corresponding β-keto-α-amino ester intermediates, which underwent spontaneous dimerization followed by air-induced aromatization to yield pyrazines. The chemoselective reduction of β-keto-α-oximino amides using baker’s yeast also afforded the corresponding pyrazines. Interestingly, both hydroximes and alkoximes gave the pyrazines by the baker’s yeast-mediated reduction via the corresponding amino ketones, the known precursors of pyrazines. The reaction was strongly dependent upon pH of reaction medium, and gave optimum yields at pH 5. These results demonstrate that pyrazines were synthesized efficiently and eco-friendly using a whole-cell biocatalytic system as an alternative to chemical reduction.

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