pH-controlled reaction divergence of decarboxylation versus fragmentation in reactions of dihydroxyfumarate with glyoxylate and formaldehyde: parallels to biological pathways

摘要

The reactions of dihydroxyfumarate with glyoxylate and formaldehyde exhibit a unique pH-controlled mechanistic divergence leading to different product suites by two distinct pathways. The divergent reactions proceed via a central intermediate (2,3-dihydroxy-oxalosuccinate, 3, in the reaction with glyoxylate and 2-hydroxy-2-hydroxymethyl-3-oxosuccinate, 14, in the reaction with formaldehyde). At pH 7-8, products (7, 8, and 15) exclusively from a decarboxylation of the intermediate are observed, while at pH 13-14, products (9, 10, and 16) solely derived from a hydroxide-promoted fragmentation of the intermediate are formed. The decarboxylative and fragmentation pathways are mutually exclusive and do not appear to coexist under the range of pH (7-14) conditions investigated. Herein, we employ a combination of quantitative C-13 NMR measurements and density functional theory calculations to provide a rationale for this pH-driven reaction divergence. These rationalizations also hold true for the reactions of dihydroxyfumarate produced in situ by the catalytic cyanide-mediated dimerization of glyoxylate. In addition, the non-enzymatic decarboxylation and fragmentation transformations of these central intermediates (3 and 14) appear to have intriguing parallels to the enzymatic reactions of oxalosuccinate and formation of glyceric acid derivatives in extant metabolism - the high and low pH mimicking the precise control exerted by the enzymes over reaction pathways. Copyright (C) 2016 John Wiley & Sons, Ltd.