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

详细信息    查看全文

• 作者：Christopher J. Butch ; Jing Wang ; Jiande Gu ; Rebeca Vindas ; Jacob Crowe ; Pamela Pollet ; Leslie Gelbaum ; Jerzy Leszczynski ; Ramanarayanan Krishnamurthy and Charles L. Liotta
• 刊名：Journal of Physical Organic Chemistry
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：29
• 期：7
• 页码：352-360
• 全文大小：1505K
• ISSN：1099-1395

文摘

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 pan class="TH_term4">intermediatepan> (2,3-dihydroxy-oxalosuccinate, , in the reaction with glyoxylate and 2-hydroxy-2-hydroxymethyl-3-oxosuccinate, , in the reaction with formaldehyde). At pH 7–8, products (, , and ) exclusively from a pan class="TH_term4">decarboxylationpan> of the pan class="TH_term4">intermediatepan> are observed, while at pH 13–14, products (, , and ) solely derived from a hydroxide-promoted pan class="TH_term4">fragmentationpan> of the pan class="TH_term4">intermediatepan> are formed. The decarboxylative and pan class="TH_term4">fragmentationpan> 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 ¹³C 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 pan class="TH_term4">dimerizationpan> of glyoxylate. In addition, the non-enzymatic pan class="TH_term4">decarboxylationpan> and pan class="TH_term4">fragmentationpan> transformations of these central intermediates ( and ) 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