New types of very efficient photolabile protecting groups based upon the [2-(2-nitrophenyi)propoxy]carbonyl (NPPOC) moiety

Based upon the photolabile [2-(2-nitrophenyl)propoxy]carbonyI group (NPPOC), a large number of modified 2-(2-nitrophenyl)propanol derivatives substituted at the phenyl ring (see 23-34 and 57-76) as well as at the side-chain (see 85-92 and 95-98) were synthesized to improve the photoreactivity of this new type of photolabile entity. The phenyl moiety was also exchanged by the naphthalenyl group (see 102,103,105,108, 110, 113, and 114), the thienyl substituent (see 115, 117, 118, and 120), and the benzothienyl substituent (see 121). The 2-(2-nitroaryl- and heteroaryl)propanols were converted with diphosgene into the corresponding carbonochloridates, which reacted subsequently with thymidine to the thymidine 5'-(protected carbonates) 123-178 as the main reaction products. In several cases, the corresponding 3'-carbonates and 3',5'-dicarbonates 179-212 were also isolated and characterized. Photolysis studies under standardized conditions (see Table) indicated that the rate of photocleavage varies in a broad range depending on the substituents. So far, the thymidine 5'-[2-(5-halo-2-nitrophenyl)propyI carbonates] 127-129, 5'-[2-(nitro[1,1'-biphenyl]3-yl)propyI carbonates] 136-139, 5'-{2-[2-nitro-5-(thianthren-1-yl)phenyl]propyl carbonate} (140), 5'-[2-(5-naphthalenyl-2-nitrophenyl)propyl carbonates] 141 and 142, and 5'-[2-(2-nitro-5-thienylphenyl)propyl carbonates] 143 and 144 showed the best properties regarding fast and uniform deprotection. Since the nucleobases of 213-215 do not influence the photocleavage features, in general, the new type of photolabile building blocks allows in form of their 3'-phosphoramidites the photolithographic formation of high-quality biochips.