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 o~-hydrogen abstraction by the photo-excited nitro group. Photolysis rates were affected by substitutions on both the phenyl ring and m-carbon, with the strongest rate enhancements caused by the presence of a methyl or second o-nitrophenyl group in the tx-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. © 1997 Elsevier Science Ltd.The use of photolabile protecting groups in nucleic acid 1-8, carbohydrate 9, and peptide 10-12 chemistry has been well established. More recently, photolabile protection of the 5'-hydroxyl of 2'-deoxyribonucleoside 3'-phosphoramidites has been employed in the solid-phase synthesis of DNA probe arrays. 13-16 Useful photolabile protecting groups must be stable to mild chemical treatments, but photolytically cleaved in high yield by irradiation at wavelengths which do not damage the protected molecule.The o-nitrobenzyl group or groups containing this photosensitive moiety have been used for photolabile protection of hydroxyl, carboxyl, amino, thiol, and carbonyl functions. 17 The removal of photolabile groups from a protected hydroxyl oxygen by irradiation at wavelengths >320 nm involves abstraction of a hydrogen from the m-methylene carbon by the excited nitro group followed by rearrangement to o-nitrosobenzaldehyde and the deprotected alcohol. In the case of the 2-nitrobenzyloxycarbonyl group, carbon dioxide is also released (Fig. 1). The quantum yield of photodeprotection may be strongly influenced by substitution on the phenyl ring or methylene carbon of the o-nitrobenzyl group. Reichmanis et al. 18 reported a 5-fold increase in quantum yield for photocleavage of the o-nitrobenzyl esters of trimethylacetic acid when the parent ester is substituted with an s-methyl group. 4247

Intramolecular Sensitization of Photocleavage of the Photolabile 2‐(2‐Nitrophenyl)propoxycarbonyl (NPPOC) Protecting Group: Photoproducts and Photokinetics of the Release of Nucleosides

“…[15,16] It is of the onitrobenzyl-type in which cleavage occurs at the benzylic carbon and the leaving moiety is an aromatic o-nitrosocarbonyl compound. [17] In photoremovable protecting groups involving the 2-(2-nitrophenyl)propoxycarbonyl (NPPOC) group, which was introduced by Pfleiderer and co-workers, [18][19][20] cleavage is due to b elimination, and formation of the reactive and problematic nitroso byproduct [21] can be suppressed by using suitable reaction conditions (Scheme 1). [22] This is probably the reason why chips of higher quality result when using the NPPOC group.…”

Synthesis of Caged Nucleosides with Photoremovable Protecting Groups Linked to Intramolecular Antennae

“…Among the photolabile protecting groups currently in use for photolithographic DNA-chip synthesis [13], the [2-(2-nitrophenyl)propoxy]carbonyl (nppoc) group (1) developed by Pfleiderer and co-workers is a prominent example [14] [15]. It reacts in excellent yield and gives rise to a good quantum yield, the only draw-back for a higher light sensitivity being its low absorption coefficient in the near UV, where illumination is usually performed with the 366-nm Hg line.…”

“…The caged thymidine 7 was derived from 2 according to [14]. Compound 2 was treated with phosgene, and the resulting chloroformate was allowed to react with thymidine, which afforded the 5'-O-protected derivative 7.…”

“…Deblocking of the OH group of 15 with Bu 4 NF in THF [26] gave the alcohol 8 in an overall yield of 42% from 10. The caged thymidine 11 was finally derived from 8 by treatment with phosgene, and reaction of the chloroformate with thymidine (34% yield) [14].…”

Synthesis of Photocleavable Linear Macromonomers by ATRP and Star Macromonomers by a Tandem ATRP−Click Reaction: Precursors to Photodegradable Model Networks

“…For example, the nitroveratroyloxycarbonyl (NVOC), which contains two methoxy substituents on the NBOC aromatic ring, is known to photocleave ∼15% faster than the NBOC group. 48 Photocleavable Star Polymers to Linear Polymers. As described above in Scheme 1B, photodegradable MNs can also be prepared by cross-linking of functional star MACs with small molecules.…”