Figure 2. Retrosynthetic analysis shows different ways leading to the same molecule. Overview about different strategies: A) Chemical synthesis via amination of 1,2-diketones and subsequent dimerization/condensation to pyrazine starting from oxidized chemical precursors. B) Combination of chemical precursor and enzymatic amination synthesis using aminotransferase (ATA-113).
An example that has been studied over centuries is 3-isobutyl-2-methoxypyrazine, a characteristic odor in grapes (Figure 3,C ), which is biosynthesized by the plant from leucine and glycine [21] or leucinamide and glyoxal [10]. Efforts have been made to identify these hypothetical precursors without final confirmation.
In general, chemical synthesis cannot convert two amino acids to a pyrazine core without a suitable catalyst. However, it is feasible to start from 1,2-diketones and diamines or aminoketones and amino aldehydes or other synthetic equivalents (Figure 2, A ). The enzymatic synthesis can combine chemical precursors and enzyme catalysis to obtain the final product (Figure 2, B ). Microbial synthesis uses the cellular network of naturally pyrazine producing microorganisms to form selectively substituted pyrazines by feeding the microorganism the necessary precursors (Figure 3, D ). The advantages and challenges of chemistry, biocatalysis and biotechnology are summarized below.