PH‐controlled reaction divergence of decarboxylation versus fragmentation in reactions of dihydroxyfumarate with glyoxylate and formaldehyde: parallels to biological pathways. (23rd February 2016)

• Record Type: Journal Article
• Authors: Butch, Christopher J.; Wang, Jing; Gu, Jiande; Vindas, Rebeca; Crowe, Jacob; Pollet, Pamela; Gelbaum, Leslie; Leszczynski, Jerzy; Krishnamurthy, Ramanarayanan; Liotta, Charles L.
• Is Part Of: Journal of physical organic chemistry. Volume 29:Number 7(2016)
• Page Start: 352
• Page End: 360
• Publication Date: 2016-02-23
• Subjects: Dihydroxyfumaric acid -- Glyoxylic acid -- pH control -- Formaldehyde; Chemistry, Physical organic -- Periodicals; 547.1
• DOI: 10.1002/poc.3542
• Languages: English
• ISSNs: 0894-3230

Abstract

Abstract: 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 centralintermediate (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, and15 ) exclusively from adecarboxylation of theintermediate are observed, while at pH 13–14, products (9, 10, and16 ) solely derived from a hydroxide‐promotedfragmentation of theintermediate are formed. The decarboxylative andfragmentation 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 13 C 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‐mediateddimerization of glyoxylate. In addition, the non‐enzymaticdecarboxylation andfragmentation transformations of these central intermediates (3 and14 ) 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 © 2016 John Wiley & Sons, Ltd. Abstract : A simple pH switch causes a strict divergence of decarboxylation or fragmentation reaction of a common intermediate, leading to distinct classes of products. Such a strict control exerted by a change of pH over reaction pathways and the nature of product formation seems to parallel the precise control exhibited by enzymes over analogous metabolic reactions.