The synthesis of nucleosides from ribose and neucleobases is endothermic, which makes the formation of the sugar–base linkage under prebiotic conditions energetically unlikely.

Judit Šponer and co-workers, Academy of Sciences of the Czech Republic, Czech Republic, have used quantum chemical calculations to discover underlying physicochemical reasons that make the glycosylation reaction between ribose and nucleobases endothermic. The model employed looked at the free energy change of the N-alkylation/N-glycosylation reactions of nucleobases.

They found that the reaction is endothermic due to the stability of the ribose lactol ring and that replacement of the glycosylic OH of ribose with a diphosphate moiety (a strategy utilized by nature) renders the N-glycosylation of nucleobases exothermic, making the glycosylic-bond formation plausible under prebiotic conditions.

• Prebiotic Routes to Nucleosides: A Quantum Chemical Insight into the Energetics of the Multistep Reaction Pathways
  J. E. Šponer, J. Šponer, M. Fuentes-Cabrera,
  Chem Eur. J. 2010, 16.
  DOI: 10.1002/chem.201002057