Sharma Pawan K, Petersen Michael, Nielsen Poul
Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, 5230 Odense M, Denmark.
J Org Chem. 2005 Jun 24;70(13):4918-28. doi: 10.1021/jo0500380.
An alpha-D-arabino configured bicyclic nucleoside strongly restricted in an E-type conformation by a 2'-3'-fused oxetane ring is synthesized. Several synthetic strategies toward the target compound are described, and the successful preparation from a D-xylose derivative is based on a ruthenium-mediated cleavage of a double bond, an S(N)2-inversion at the 2-position to give an arabino-configuration, nucleobase coupling, and finally ring closure to give the oxetane ring. The E-type conformation is confirmed by molecular modeling and NMR. The nucleoside is incorporated into short alpha-DNA sequences. In a mixed pyrimidine context, these recognize complementary parallel RNA-sequences with mainly increased affinity and complementary parallel DNA-sequences with decreased affinity. The present bicyclic analogue represents the first conformationally restricted alpha-DNA-analogue to improve nucleic acid recognition in mixmers with alpha-DNA monomers.
合成了一种由α-D-阿拉伯糖构型的双环核苷，其通过2'-3'-稠合的氧杂环丁烷环强烈限制在E型构象中。描述了几种合成目标化合物的策略，从D-木糖衍生物成功制备该化合物基于钌介导的双键裂解、2位的S(N)2-构型翻转以得到阿拉伯糖构型、核苷酸碱基偶联，最后闭环形成氧杂环丁烷环。通过分子建模和核磁共振证实了E型构象。该核苷被掺入短的α-DNA序列中。在混合嘧啶环境中，这些序列识别互补的平行RNA序列时亲和力主要增加，识别互补的平行DNA序列时亲和力降低。目前的双环类似物代表了第一种构象受限的α-DNA类似物，用于改善与α-DNA单体的混合体中的核酸识别。
