A new construct for the anti conformational locking of nucleosides: the dioxomethine transglycosidic tether

Two members of a new class of anti conformationally locked 2'-deoxynucleoside mimics were synthesized starting from uridine through key 1-(β-D-arabinofuranosyl)uracil-6-carboxaldehyde intermediates.O5'-Mesylation of 1-(β-D-arabinofuranosyl)uracil-6-carboxaldehyde (5c) followed by pyridine-mediated transglycosidic displacement by the dominant 7,O2'-cyclic hemiacetal gave the locked 2',5'-dideoxyuridine mimic (7).Transglycosidic transacetalation in the 7,O2'-cyclic hemiacetal of 1-(5-deoxy-5,5-dimethoxy-β-D-arabinofuranosyl)uracil-6carboxaldehyde (18) gave the locked O5'-methyl-2'-deoxyuridine mimic (6b).These transglycosidic dioxomethine tether constructions involve proximity-assisted displacement reactions and provide an entry into new, highly biomimetic, anti conformationally locked 2'deoxynucleoside mimics for use as probes of conformation-activity relationships.