The 5′,6-Oxomethylene Transglycosidic Tether for Conformational Restriction of Pyrimidine Ribonucleosides. Investigation of 6-Formyl- and 6-(Hydroxymethyl)uridine 5′-Carboxaldehydes

In an effort to develop a new motif for the transglycosidic tethering of the pyrimidine nucleoside framework, the 2′,3′-O-isopropylidenated and unprotected versions of 6-formyl- and 6-(hydroxymethyl)uridine 5′-carboxaldehyde were prepared and these were examined for their ability to adopt 5′,6-oxomethylene tethered solution structures. In aqueous solution, the 2′,3′-O-isopropylidenated nucleosides readily generated spiro-dihydrouridines via proximity-induced transglycosidic intramolecular reactions. In stark contrast, their unprotected counterparts existed mainly as the untethered aldehyde hydrates. Based on these findings, the 5′,6-oxomethylene transglycosidic tether appears to constitute a useful conformational restriction motif for the pyrimidine ribonucleoside framework, but only when the 5′-OH group is functionalized.