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 cycloaddition 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 (15%), 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.