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 th e pyrimidine nucleoside framework, the 2',3'-O-isopropylidenated and unprot ected versions of 6-formyl- and 6-(hydroxymethyl)uridine 5'-carboxaldehyde were prepared and these were examined for their ability to adopt 5',6-oxome thylene tethered solution structures. In aqueous solution, the 2',3'-O-isop ropylidenated nucleosides readily generated spiro-dihydrouridines via proxi mity-induced transglycosidic intramolecular reactions. In stark contrast, t heir unprotected counterparts existed mainly as the untethered aldehyde hyd rates. Based on these findings, the 5',6-oxomethylene transglycosidic tethe r appears to constitute a useful conformational restriction motif for the p yrimidine ribonucleoside flamework, but only when the 5'-OH group is functi onalized. (C) 2000 Elsevier Science Ltd. All rights reserved.