Prebiotic Photochemical Coproduction of Purine Ribo- and Deoxyribonucleosides.

Nicholas J. Green,John D. Sutherland,Ziwei Liu,David A. Russell,Jianfeng Xu

doi:10.1021/jacs.1c07403

Nicholas J. Green, John D. Sutherland + Show 3 more

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https://doi.org/10.1021/jacs.1c07403

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Abstract

The hypothesis that life on Earth may have started with a heterogeneous nucleic acid genetic system including both RNA and DNA has attracted broad interest. The recent finding that two RNA subunits (cytidine, C, and uridine, U) and two DNA subunits (deoxyadenosine, dA, and deoxyinosine, dI) can be coproduced in the same reaction network, compatible with a consistent geological scenario, supports this theory. However, a prebiotically plausible synthesis of the missing units (purine ribonucleosides and pyrimidine deoxyribonucleosides) in a unified reaction network remains elusive. Herein, we disclose a strictly stereoselective and furanosyl-selective synthesis of purine ribonucleosides (adenosine, A, and inosine, I) and purine deoxynucleosides (dA and dI), alongside one another, via a key photochemical reaction of thioanhydroadenosine with sulfite in alkaline solution (pH 8–10). Mechanistic studies suggest an unexpected recombination of sulfite and nucleoside alkyl radicals underpins the formation of the ribo C2′–O bond. The coproduction of A, I, dA, and dI from a common intermediate, and under conditions likely to have prevailed in at least some primordial locales, is suggestive of the potential coexistence of RNA and DNA building blocks at the dawn of life.

Highlights

The hypothesis that life on Earth may have started with a heterogeneous nucleic acid genetic system including both RNA and DNA has attracted broad interest
With a mixture of ribo- and deoxyribonucleosides 10 and 11 in hand, we evaluated their reactivity in this context to see if we might generate inosine 9, a potential surrogate for guanosine in the deoxyribofuranosides of adenine and hypoxanthine (8, 1, 9, and 2) are available concomitantly, raising the possibility that these nucleosides formed components of a primordial genetic alphabet, surviving the test of evolution to varying degrees
The most closely related example we found was the suggestion by Kolker and Lapworth[34] that alongside reaction at S to form sulfonates, sulfite radicals may react with some alkenes at O to form sulfites

Summary

Introduction

The hypothesis that life on Earth may have started with a heterogeneous nucleic acid genetic system including both RNA and DNA has attracted broad interest. Nitrosative desulfurization and partial deamination were previously shown to convert deoxyadenosine 1 and its 8-mercapto precursor 10 to a mixture of dA and dI.[9] With a mixture of ribo- and deoxyribonucleosides 10 and 11 in hand, we evaluated their reactivity in this context to see if we might generate inosine 9, a potential surrogate for guanosine in the deoxyribofuranosides of adenine and hypoxanthine (8, 1, 9, and 2) are available concomitantly, raising the possibility that these nucleosides formed components of a primordial genetic alphabet, surviving the test of evolution to varying degrees.

Results

Conclusion