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. 2012 Feb 22;134(7):3577-89.
doi: 10.1021/ja211383c. Epub 2012 Feb 10.

Exploratory experiments on the chemistry of the "glyoxylate scenario": formation of ketosugars from dihydroxyfumarate

Vasudeva Naidu Sagi  1 , Venkateshwarlu Punna, Fang Hu, Geeta Meher, Ramanarayanan Krishnamurthy
Affiliations
Free PMC article

Exploratory experiments on the chemistry of the "glyoxylate scenario": formation of ketosugars from dihydroxyfumarate

Vasudeva Naidu Sagi et al. J Am Chem Soc. .
Free PMC article

Abstract

In the context of a "glyoxylate scenario" of primordial metabolism, the reactions of dihydroxyfumarate (DHF) with reactive small molecule aldehydes (e.g., glyoxylate, formaldehyde, glycolaldehyde, and glyceraldehyde) in water were investigated and shown to form dihydroxyacetone, tetrulose, and the two pentuloses, with almost quantitative conversion. The practically clean and selective formation of ketoses in these reactions, with no detectable admixture of aldoses, stands in stark contrast to the formose reaction, where a complex mixture of linear and branched aldoses and ketoses are produced. These results suggest that the reaction of DHF with aldehydes could constitute a reasonable pathway for the formation of carbohydrates and allow for alternative potential prebiotic scenarios to the formose reaction to be considered.

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Figures

Scheme 1
Scheme 1. Condensation Reaction between 0.4 M (Li or Cs Salts of) DHF (2) and 0.4 M Sodium Glyoxylate (1) Leading to the Formation of Dihydroxyacetone (4) and a (∼1:1) Diastereomeric Mixture of Pentulosonic Acid (3a + 3b) as Deciphered by Monitoring with 13C NMR Spectroscopy
13C NMR chemical shifts (δ, ppm) are shown in the Cs series.
Figure 1
Figure 1
13C NMR (150 MHz, H2O/D2O) of the reaction mixture from Cs2DHF with cesium glyoxylate (0.5 M, 1:1) after 20 h at rt, showing the 1:1 mixture of pentulosonic acid diastereomers (3a + 3b) and dihydroxyacetone (4).
Scheme 2
Scheme 2. The Reaction of 0.4 M DHF with 1 Equiv of Doubly 13C-Labeled Glyoxylate (as Followed by 13C NMR Spectroscopy)
13C-labeled glyoxylate contains 1.5% oxalic acid and 3% glycolic acid. 13C NMR chemical shifts (δ, ppm) are as indicated; d = doublet (J ≈ 45 Hz), s = singlet.
Scheme 3
Scheme 3. Reaction of DHF and 13C-Labeled Glyoxylate under Dilute (0.04 M) Conditions, with 13C NMR Chemical Shifts (δ, ppm)
Scheme 4
Scheme 4. Reaction of DHF with Formaldehyde Leads to Formation of Dihydroxyacetone or Tetrulose As Determined by 13C NMR Spectroscopy
Acidification leads to the formation of (hydrated) 2,3-diketobutanol (12). 13C NMR chemical shifts (δ, ppm) are indicated.
Scheme 5
Scheme 5. Reaction Pathway of 1.0 Equiv of DHF with 1.0 Equiv of Glycolaldehyde Leading to the Formation of Tetrulose As Discerned by 13C NMR Spectroscopy
13C NMR chemical shifts (δ, ppm) are shown.
Figure 2
Figure 2
13C NMR spectrum (150 MHz, drops of D2O) of the reaction mixture of 0.1 M Li2DHF + 0.1 M glycolaldehyde (1:1) at rt, after 20 h. Peak at 160.95 ppm is HCO3–.
Scheme 6
Scheme 6. Formation of Pentuloses from the Reaction of DHF with Glyceraldehyde by the Reaction Pathway As Inferred by Monitoring with 13C NMR Spectroscopy
Chemical shifts (δ, ppm) are shown.
Figure 3
Figure 3
13C NMR (150 MHz, drops of D2O) of reaction mixture supernatant after overnight at rt (0.33 M Li2DHF + 0.33 M glyceraldehyde in degassed H2O + ZnCl2).
Figure 4
Figure 4
1H NMR (600 MHz, D2O) of crude product (0.33 M Li2DHF + 0.33 M glyceraldehyde in degassed H2O + ZnCl2).
Figure 5
Figure 5
Comparison of the 1H NMR spectral data (D2O) documenting the formation of the two pentuloses in the reaction of DHF and dl-glyceraldehyde. top (blue), authentic ribulose; middle (green), crude reaction mixture; bottom (red), authentic xylulose.
Scheme 7
Scheme 7. Reaction of DHA with DHF (as Followed by 13C NMR Spectroscopy)
13C NMR chemical shifts (δ, ppm) are indicated.
Scheme 8
Scheme 8. The “Expanded” Reaction Spectrum of Aqueous Chemistry of DHF
M = H, Li, Cs, or Mg. The formation of dioxosuccinate may not be relevant in the context of potential prebiotic chemistry.
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