The Pyruvate Aldol Condensation Product: A Metabolite that Escaped Synthetic Preparation for Over a Century

The homo-aldol condensation product of pyruvate, 2-methyl-4-oxopent-2-enedioic acid (OMPD) has been recently implicated as a catabolic intermediate in the bacterial degradation of lignin and previously identified from other biological sources in reports ranging over sixty years. Yet, while a preparation of the pyruvate aldol-product precursor, 4-hydroxy-4-methyl-2-oxoglutaric acid (HMOG) was first reported in 1901, there has not been a complete published synthesis of OMPD. Analysis of reaction mixtures have helped identify that it is zymonic acid, the lactone of HMOG, that is the direct precursor to OMPD. The reaction appears to proceed through an acid or base mediated ring opening that does not involve formal lactone hydrolysis. In addition to a preparative protocol we provide a proposed mechanism for the formation of methylsuccinic acid that arises from the non-oxidative decarboxylation of OMPD. Lastly, we report on the relative stability of the possible isomers of the condensation product and find that at all pH values, Z-OMPD is the most abundant.