Acyclic nucleosides are potential antiviral and antitumor agents. In this work, their preparation through a novel chemoenzymatic procedure involving the N-alkylation of a nu-
N-2-oxoethyl derivatives of nucleobases are useful starting materials for the preparation of potentially active nucleoside analogues. The 1 HNMR, 13 CNMR, DEPT and ESI-MS spectra of adenine and thymine N-2oxoethyl derivatives reveal that the different species in equilibrium exist mainly in two forms: aldehyde and hydrate. The NMR spectra show that the equilibrium is shifted towards the hydrate form in water-DMSO 2:1, giving equilibrium constants of 8.3 and 5.3 for adenine and thymine derivatives, respectively. ESI-MS experiments show the dependence of equilibrium shift on pH: in the case of the thymine derivative, the effect on the equilibrium is more important than in the case of the adenine derivative; this difference is explained considering different protonation sites in both structures. All assumptions are supported by theoretical calculations, which suggest the important role played by solvent in the stabilization of molecular structures and equilibrium shift. All aspects analyzed in this work are very important in order to understand the further reactivity of these nucleobase derivatives.
Acyclic nucleosides, which exhibit significant antiviral activity, are usually synthesised using traditional chemical strategies. However, the efficient and selective formation of carbon‐carbon bonds using small organic molecules as catalysts provides a promising alternative route for the sustainable synthesis of this family of compounds. Following this organocatalytic strategy, 5‐(adenyl, thyminyl and cytosyl)‐4‐hydroxy‐2‐pentanones were prepared by the pyrrolidine catalysed reaction between the 2‐oxoethyl derivative of the corresponding nucleobases and acetone. In order to investigate the keto‐enol equilibrium of these compounds in basic media, H‐D exchange studies were carried out by 1H and 13C NMR spectroscopy. The obtained results suggest that the mechanism by which this exchange occurs is of first order with respect to all the substrates, but of second order with regard to pyrrolidine in the case of the cytosine and adenine derivatives and of first order for the thymine analogue. Theoretical calculations of the structures involved in this equilibrium also suggest that the stability of the different ionic intermediates depends on the pKa of the corresponding nucleobases.
involving an aldol condensation of aldehydes of various nucleobases catalyzed by a dihydroxyacetone phosphate‐dependent aldolase (rabbit muscle aldolase)
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