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.