New types of very efficient photolabile protecting groups based upon the [2-(2-nitrophenyi)propoxy]carbonyl (NPPOC) moiety
New types of very efficient photolabile protecting groups based upon the [2-(2-nitrophenyi)propoxy]carbonyl (NPPOC) moiety
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DOI：
10.1002/hlca.200490060
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发表时间：
2004-01-01
影响因子：
1.8
通讯作者：
Pfleiderer, W
中科院分区：
文献类型：
--
作者：
Bühler, S;Lagoja, I;Pfleiderer, W
基于光不稳定的[2-（2-硝基苯基）丙氧基]羰基（NPPOC），合成了大量在苯环（参见23-34和57-76）以及侧链（参见85-92和95-98）处取代的改性2-（2-硝基苯基）丙醇衍生物，以改善这种新型光不稳定实体的光反应性。苯基部分也被萘基（见102、103、105、108、110、113和114）、噻吩基取代基（见115、117、118和120）和苯并噻吩基取代基（见121）取代。用双光气将2-（2-硝基芳基-和杂芳基）丙醇转化为相应的氯甲酸酯，随后与胸苷反应，得到胸苷5 ′-（受保护的碳酸酯）123-178作为主要反应产物。在几种情况下，还分离和表征了相应的3 '-碳酸酯和3'，5 '-二碳酸酯179-212。在标准化条件下的光解研究（见表）表明，光裂解速率在很宽的范围内变化，这取决于取代基。到目前为止，胸苷5 '-[2-（5-卤代-2-硝基苯基）丙基碳酸酯] 136-139，5 '-{2-[2-硝基-5-（三氟甲基）苯基]-2-甲基-苯基}-3-（硝基[1，1'-联苯]-3-基）丙基}碳酸酯]（噻喃-1-基）苯基]丙基碳酸酯}（140），[5-（5-萘基-2-硝基苯基）丙基碳酸酯] 141和142以及5 '-[2-（2-硝基-5-噻吩基苯基）丙基碳酸酯] 143和144显示出关于快速和均匀脱保护的最佳性质。由于213-215的核碱基不影响光裂解特征，因此通常，新型的光不稳定结构单元以其3 '-亚磷酰胺的形式允许高质量生物芯片的可重复形成。
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.