PHOTOLABILE PROTECTING GROUPS FOR NUCLEOSIDES - SYNTHESIS AND PHOTODEPROTECTION RATES

o-Nitrobenzyloxycarbonyl and a number of related groups have been test ed for the photolabile protection of nucleoside 5'-hydroxyls. The rate s 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)ethoxycarb onyl group and its derivatives were found to be removed approximately 2-fold faster than the corresponding o-nitrobenzyloxycarbonyl group, p ossibly due to an increased rare of alpha-hydrogen abstraction by the photo-excited nitro group. Photolysis rates were affected by substitut ions on both the phenyl ring and alpha-carbon, with the strongest rate enhancements caused by the presence of a methyl or second o-nitrophen yl group in the alpha-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 photode protection. In general, substitutions at other positions on the phenyl ring had less effect on photolysis rates. (C) 1997 Elsevier Science L td.