Selective Prebiotic Synthesis of α-Threofuranosyl Cytidine by Photochemical Anomerization

The structure of life's first genetic polymer is a question of intense ongoing debate. The RNA world theory suggests RNA was life's first nucleic acid. However, ribonucleotides are complex chemical structures, and simpler nucleic acids, such as threose nucleic acid (TNA), can carry genetic information. In principle, nucleic acids like TNA could have played a vital role in the origins of life. The advent of any genetic polymer in life requires synthesis of its monomers. Here we demonstrate a high-yielding, stereo-, regio- and furanosyl-selective prebiotic synthesis of threo-cytidine 3, an essential component of TNA. Our synthesis uses key intermediates and reactions previously exploited in the prebiotic synthesis of the canonical pyrimidine ribonucleoside cytidine 1. Furthermore, we demonstrate that erythro-specific 2 ',3 '-cyclic phosphate synthesis provides a mechanism to photochemically select TNA cytidine. These results suggest that TNA may have coexisted with RNA during the emergence of life.

Automated summary

The debate over the structure of life's first genetic polymer continues, with the RNA world theory proposing RNA as the first nucleic acid. However, simpler nucleic acids like TNA could also have carried genetic information. The study demonstrates a high-yielding, selective prebiotic synthesis of a key component of TNA, suggesting that TNA may have coexisted with RNA during the emergence of life.