Highly efficient photolabile protecting groups with intramolecular energy transfer.

DNA chips are widely used for genomic analysis. Currently, high-density DNA chips can be synthesized with up to several hundred thousand different spots on an area of 1 cm. In principle, the complete human genome can be probed with such a chip. The required high spot densities can be achieved by photolithographic in situ DNA-chip synthesis. In this method, the oligonucleotides are synthesized step by step from protected nucleoside phosphitamides using photolithography with masks or micromirror arrays as suitable means for achieving parallel spatial addressability. This technique requires photolabile protecting groups of high light sensitivity that release their substrate (in this case a nucleotide) in nearly quantitative yield. For the protecting groups currently in use for DNA-chip synthesis, the light sensitivity, suitably characterized by the product ef of the absorption coefficient and the photochemical quantum yield, reaches only moderate values. The widely used [(a-methyl-2-nitropiperonyl)oxy]carbonyl (MeNPOC) group has a reasonable absorption coefficient at the wavelengths usually applied (in practice preferentially the mercury line at l= 366 nm, eMeOH,366 nm 2500 m 1 cm ), but the photochemical deprotection yield is quite small (3% in MeOH). In contrast, the 2-(2nitrophenyl)propoxycarbonyl (NPPOC) protecting group, the reaction of which is represented in Scheme 1, shows a