Prebiotic synthesis of simple sugars by photoredox systems chemistry

Abstract

A recent synthesis of activated pyrimidine ribonucleotides under prebiotically plausible conditions relied on mixed oxygenous and nitrogenous systems chemistry. As it stands, this synthesis provides support for the involvement of RNA in the origin of life, but such support would be considerably strengthened if the sugar building blocks for the synthesis--glycolaldehyde and glyceraldehyde--could be shown to derive from one carbon feedstock molecules using similarly mixed oxygenous and nitrogenous systems chemistry. Here, we show that these sugars can be formed from hydrogen cyanide by ultraviolet irradiation in the presence of cyanometallates in a remarkable systems chemistry process. Using copper cyanide complexes, the process operates catalytically to disproportionate hydrogen cyanide, first generating the sugars and then sequestering them as simple derivatives.

Figure 1. Homologation routes to simple sugars from formaldehyde 1

a, Direct homologation of formaldehyde 1 is problematic, because the first dimerization step (dashed) requires umpolung, and because the trimer is more stable as the ketose 4 than the aldose 3 under conditions where 3 can be formed from 1 and 2. b, Kiliani–Fischer homologation of 1 in conventional synthetic chemistry involves favourable formation of the cyanohydrin 6 by reaction of 1 with hydrogen cyanide 5, followed by the selective reduction of 6 using very specific conditions.

Figure 2. Photoredox cycling of copper cyanide complexes in the presence of hydrogen cyanide 5

Each turn of the cycle results in the oxidation of two molecules of hydrogen cyanide 5 to cyanogen 11, with the concomitant production of two protons and two hydrated electrons. The photoxidation of the tricyanocuprate(I) species 8 to tricyanocuprate(II) 9 is inferred because the corresponding dicyanocuprate(I) is not photoactive at 254 nm, and, according to stability constant calculations, the tetracyanocuprate(I) is a very minor species. Dimerization of 9 to the binuclear complex 10 and reductive elimination of cyanogen 11 giving dicyanocuprate(I) 12 is suggested by the kinetics of the decomposition of copper(II) cyanide complexes. Finally, conversion of dicyanocuprate(I) 12 to tricyanocuprate(I) 8 is suggested by the aforementioned photoinactivity of 12 and stability constant data, and the fact that a cycle is clearly operative.

Figure 3. ¹³C-NMR analysis of the organic intermediates and products formed by the photoredox cycling of copper cyanide complexes in the presence of hydrogen cyanide 5

a, Time course analysis showing the complexity of the system increasing and then decreasing. Question marks indicate inferred assignments. b, Enlargement of the spectrum of the photochemical products after 7 h (middle) compared to the ¹³C-NMR spectra of 13 (upper) and 14 (lower), the products of reaction of potassium cyanate with glycolaldehyde 2 and glyceraldehyde 3, respectively.

Figure 4. ¹H-NMR analysis of photochemical products

a–c, ¹H-NMR spectrum of the products after an 8 h reaction without intermediary sampling (b) as compared to the ¹H-NMR spectra of 13 (a) and 14 (c). Small chemical shift differences are thought to be due to pH differences, and are not seen in spiked spectra (see Supplementary Information).

Figure 5. Disproportionation of hydrogen cyanide 5 and ensuing systems chemistry

a,b, The organic chemistry that occurs when the inorganic photoredox cycling of Fig. 2 operates can be loosely described in two stages as in a and b.