Production of Tartrates by Cyanide-Mediated Dimerization of Glyoxylate: A Potential Abiotic Pathway to the Citric Acid Cycle

Abstract

An abiotic formation of meso- and dl-tartrates in 80% yield via the cyanide-catalyzed dimerization of glyoxylate under alkaline conditions is demonstrated. A detailed mechanism for this conversion is proposed, supported by NMR evidence and 13C-labeled reactions. Simple dehydration of tartrates to oxaloacetate and an ensuing decarboxylation to form pyruvate are known processes that provide a ready feedstock for entry into the citric acid cycle. While glyoxylate and high hydroxide concentration are atypical in the prebiotic literature, there is evidence for natural, abiotic availability of each. It is proposed that this availability, coupled with the remarkable efficiency of tartrate production from glyoxylate, merits consideration of an alternative prebiotic pathway for providing constituents of the citric acid cycle.

Anchimeric‐Assisted Spontaneous Hydrolysis of Cyanohydrins Under Ambient Conditions: Implications for Cyanide‐Initiated Selective Transformations

“…For example, when a solution of glyoxylic acid at pH 7 was treated with 0.5 equiv. of NaCN, the pH of the solution rose to pH 12.5 and the cyanohydrin adduct 5 was formed, but was accompanied by side reactions and a messy 13 C NMR spectrum (Supporting Information Figure S12) indicative of interference from Cannizzaro type reactions or deoxalation reactions. In another experiment, the glyoxylate–cyanohydrin adduct 5 was separately formed at pH 6.5, and the pH was adjusted to pH≈10.5 (Supporting Information Figure S13).…”

“…Recently, we reported that reaction of glyoxylate 1 with catalytic cyanide at pH 13 led to the production tartrate 2 and oxalate 3 in high yields in a novel deoxalation reaction (Scheme a) . Within a prebiotic context, however, such a high pH could be considered problematic.…”

Formation of Glyoxylic Acid in Interstellar Ices: A Key Entry Point for Prebiotic Chemistry

“…[1] Parts of this scenario have been verified, for instance,the formation of the formal glyoxylate dimer dihydroxyfumarate (DHF, 2)b y treating glyoxylate with hydrogen cyanide (HCN) in an Umpolung reaction that further reacts to form tartrate,which might serve as ap recursor for oxaloacetic acid and pyruvate; [2] both are constituents of the citric acid cycle.G lycine (3), the simplest amino acid, can easily form from the reductive amination of 1 (Scheme 1). [1] Parts of this scenario have been verified, for instance,the formation of the formal glyoxylate dimer dihydroxyfumarate (DHF, 2)b y treating glyoxylate with hydrogen cyanide (HCN) in an Umpolung reaction that further reacts to form tartrate,which might serve as ap recursor for oxaloacetic acid and pyruvate; [2] both are constituents of the citric acid cycle.G lycine (3), the simplest amino acid, can easily form from the reductive amination of 1 (Scheme 1).…”

“…[6] Furthermore,t he authors reported the formation of acyclicketoses up to aC 5 chain length in the reaction of DHF with glycolaldehyde (4), glyceraldehyde (5), and glyoxylate. [8] Decarboxylation of 1 in the gas-phase yields hydroxymethylene (6,H -C -OH), which has been identified in an inert gas matrix at cryogenic temperatures around 10 K. [9] Even at these temperatures, 6 undergoes a [ 1,2]H-shift via tunneling to form formaldehyde (7)with afirst order tunneling half-life of around 2h. [8] Decarboxylation of 1 in the gas-phase yields hydroxymethylene (6,H -C -OH), which has been identified in an inert gas matrix at cryogenic temperatures around 10 K. [9] Even at these temperatures, 6 undergoes a [ 1,2]H-shift via tunneling to form formaldehyde (7)with afirst order tunneling half-life of around 2h.…”

Citric Acid and the RNA World

“…[14] Instead, related compounds with potential Mg 2+ chelating properties, such as tartrate (Figure 2b), could have been generated by simpler prebiotic processes. [15] Inefficient prebiotic syntheses of such compounds would have created a selection pressure for RNA world organisms to evolve catalytic RNAs that catalyze limiting steps in the synthesis of such protective agents. In this way, sub-sets of the citric acid cycle could have operated in RNA world organisms to later evolve into today's citric-acid-centered metabolisms.…”