The synthesis and conformation of 2′- and 3′-hypermodified tricyclic nucleosides and their use in the synthesis of novel 2′- or 3′-isomeric 4(7)-substituted isoxazolidine-nucleosides

Abstract

Intramolecular 1,3-dipolar cycloadditon reactions of a number of C -alkenyl nitrones of nucleoside derivatives 7, 9, 19 and 28 afforded 2′- and 3′-hypermodified tricyclic nucleoside derivatives 10 (56%), 11 (43%), 20(91%) and 29 (75%), respectively. The solution structures of these tricyclic nucleoside derivatives have been investigated using the 3J HH ( 1H at 500 MHz) and the NMR-derived torsion angle constrained energy minimizations with the aid of MacroModel's AMBER force field. Subsequent Tamao oxidation of the hypermodified nucleoside derivatives 20 and 29 gave spiro-4(7)-substituted isoxazolidine-nucleoside derivatives 21 and 30, respectively.