Photolabile Protecting Groups for Nucleosides: Synthesis and Photodeprotection Rates.

Abstract o-Nitrobenzyloxycarbonyl and a number of related groups have been tested for the photolabile protection of nucleoside 5'-hydroxyls. The rates of photodeprotection were found to vary by approximately 17-fold in a series of 5'-O-protected thymidine derivatives irradiated at 365 nm under identical conditions. The homologous 2-(o-nitrophenyl)ethoxycarbonyl group and its derivatives were found to be removed approximately 2-fold faster than the corresponding o-nitrobenzyloxycarbonyl group, possibly due to an increased rate of α-hydrogen abstraction by the photo-excited nitro group. Photolysis rates were affected by substitutions on both the phenyl ring and α-carbon, with the strongest rate enhancements caused by the presence of a methyl or second o-nitrophenyl group in the α-position. Among the ring-substituted derivatives studied, o-nitro and o-iodo had the strongest enhancement effects on photodeprotection, while an o-fluoro group reduced the rate of photodeprotection. In general, substitutions at other positions on the phenyl ring had less effect on photolysis rates.