FACILE ADDITION OF HYDROXYLIC NUCLEOPHILES TO THE FORMYL GROUP OF URIDINE-6-CARBOXALDEHYDES

The ''instability'' previously ascribed to the tri-O-protected 6-formyluridines has been shown to be due to a facile hydration of the aldehyde functionality. Using an efficient protecting group strategy, 2',3',5'-tris-O-(methoxymethyl)uridine-6-carboxaldehyde (2) was prepared in two steps from uridine. Aldehyde 2 was shown to undergo a reversible hydration reaction in (CD3)2SO solution to give the gem-diol 3, according to extensive H-1 and C-13 1D and 2D NMR spectroscopic analyses. This gem-diol was the sole structure detected in D2O solution. The diethyl acetal derivative 4 provided spectral data for comparison to that of 3. Compound 2 afforded diastereomeric hemiacetal products upon treatment with alcohols, and deprotection of 2 afforded the heretofore unknown uridine-6-carboxaldehyde, which was found to exist as a 1:10 mixture of free aldehyde A and a 5'-cyclic hemiacetal structure D in dry (CD3)2SO solution, but as a 1:2 mixture of a 5'-cyclic hemiacetal structure D and the gem-diol B in D2O solution, by NMR.