7,5′-O-Dibenzylinosines: Synthesis and Studies on Their Conformational Properties

Abstract

Reaction of 2',3'-O-isopropylidene inosine with benzyl bromide (1 h, rt) led to the 1,5'-O-dibenzylderivative 4, but by increasing the reaction time or the temperature, compound 4 is further transformed into the 1,7,5'-O-tribenzylinosine derivative 5. Similarly, the 7-methyl-1,5'-O-dibenzylderivative 6 has been synthesized from 4. The 1H-NMR spectra of 5 and 6 showed peculiar chemical shifts for geminal protons (H5' and H5'' of the ribose, and the CH2 of the benzyl groups). Preliminary NMR studies have been performed, including NOESY experiments that point toward the predominant existence of conformers that are stabilized by an electrostatic interaction between the positively charged imidazole of the base moiety and the high electron density of the 5'-benzyl substituent.

Intramolecular Cation−π Interactions As the Driving Force To Restrict the Conformation of Certain Nucleosides

“…This study started within our research program on purine nucleosides. 23 While performing the synthesis of 1-benzyl-5 0 -O-benzyl-2 0 ,3 0 -O-isopropylideneinosine 23 (1, Figure 2a), the desired compound was obtained together with a novel derivative identified as 1,7-dibenzyl-5 0 -O-benzyl-2 0 ,3 0 -O-isopropylideneinosine bromide 24 (2, Figure 2b).…”