Nagatsugi F, Uemura K, Nakashima S, Maeda M, Sasaki S
Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Nucleic Acids Symp Ser. 1995(34):171-2.
We have previously synthesized 6-vinylated guanosine derivatives by new Pd(0)-catalyzed cross-coupling reaction using guanosine 6-O-tosylate and vinyltributyl-stannane. Its potentials as a cross-linking agent have been demonstrated by adduct formation with guanosine and cytidine. But these 6-vinylated derivatives could not be incorporated to oligonucleotide because of chemical instability. In this paper, we report new deoxyguanosine derivatives with substituted olefin (2 and 3), which were designed to control the reactivity of vinyl functional group. Although either 2 or 3 did not formed the adducts with nucleobases, these compounds reacted with hydroxylamine hydrochloride in the presence of acid catalyst. The reactivity was in the order of 1 > 2 > 3. These results suggest that new guaosine derivatives (2 and 3) have moderate reactivity toward nucleophiles and are expected to be stable in incorporating into oligonucleotides as a cross-linking agent.
我们之前通过使用鸟苷6-O-甲苯磺酸酯和乙烯基三丁基锡，经新型钯(0)催化的交叉偶联反应合成了6-乙烯基化鸟苷衍生物。其作为交联剂的潜力已通过与鸟苷和胞苷形成加合物得到证明。但由于化学不稳定性，这些6-乙烯基化衍生物无法掺入寡核苷酸中。在本文中，我们报道了带有取代烯烃的新型脱氧鸟苷衍生物（2和3），其设计目的是控制乙烯基官能团的反应性。尽管2或3均未与核碱基形成加合物，但这些化合物在酸催化剂存在下与盐酸羟胺反应。反应活性顺序为1>2>3。这些结果表明，新型鸟苷衍生物（2和3）对亲核试剂具有适度的反应性，有望作为交联剂稳定地掺入寡核苷酸中。
