Photolabile protecting groups for nucleosides: Synthesis and photodeprotection rates

• Published in: Tetrahedron Vol. 53; no. 12; pp. 4247 - 4264
• Main Authors: Hasan, Ahmad, Stengele, Klaus-Peter, Giegrich, Heiner, Cornwell, Paul, Isham, Kenneth R., Sachleben, Richard A., Pfleiderer, Wolfgang, Foote, Robert S.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 24.03.1997; Elsevier
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; 2'-HYDROXYL GROUP; ORGANIC-SYNTHESIS; NUCLEOTIDES; PHOSPHOTRIESTER APPROACH; SOLID-PHASE SYNTHESIS; SEQUENCE; ORTHO-NITROBENZYL PROTECTION; PHOTOLYSIS; TRANSFER RIBONUCLEIC-ACIDS
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/S0040-4020(97)00154-3

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. The synthesis and photodeprotection rates of a series of thymidine derivatives with 5′-photolabile protecting group are described.