Nucleic acids are central to information transfer and replication in living systems, providing the molecular foundations of Darwinian evolution. Here we report that prebiotic acetylation of the non-natural, but prebiotically plausible, ribonucleotide α-cytidine-5'-phosphate, selectively protects the vicinal diol moiety. Vicinal diol acetylation blocks oxazolidinone formation and prevents C2'-epimerization upon irradiation with UV-light. Consequently, acetylation enhances (4-fold) the photoanomerization of α-cytidine-5'-phosphate to produce the natural β-pyrimidine ribonucleotide-5'-phosphates required for RNA synthesis.