Sekine M, Kurasawa O, Shohda K, Seio K, Wada T
Department of Life Science, Tokyo Institute of Technology, Yokohama, Japan.
J Org Chem. 2000 Oct 6;65(20):6515-24. doi: 10.1021/jo0002588.
This paper describes the design and synthesis of a conformationally rigid dimer building block Umpc3Um as a chiral center at the phosphate group with the S/N junction where c3 refers to a propylene bridge linked between the uracil 5-position and 5'-phosphate group of pUm. The extensive H1 NMR analysis of Umpc3Um suggests that the 5'-upstream Um has predominantly a C2'-endo conformation and the pc3Um moiety exists almost exclusively in a C3'-endo conformation. The absolute configuration of the diastereomers Umpc3Um(fast) (8a) and Umpc3Um(slow) (8b) was determined by CD spectroscopy as well as computer simulations. The oligonucleotides U4[Umpc3Um(fast)]U4 (13a) and U4[Umpc3Um(slow)]U4 (13b) incorporating 8a and 8b were synthesized by use of the phosphoramidite building blocks 11a and 11b, respectively. The Tm experiments of the duplexes formed between these modified oligomers and the complementary oligomers imply that the modified oligomer 13a having Umpc3Um(fast) has the Sp configuration at the chiral phosphoryl group.
本文描述了一种构象刚性二聚体结构单元Umpc3Um的设计与合成，该结构单元在磷酸基团处具有手性中心以及S/N连接，其中c3指连接在尿嘧啶5位与pUm的5'-磷酸基团之间的亚丙基桥。对Umpc3Um进行的广泛的¹H NMR分析表明，5'-上游的Um主要具有C2'-内型构象，而pc3Um部分几乎仅以C3'-内型构象存在。通过圆二色光谱以及计算机模拟确定了非对映异构体Umpc3Um（快速）（8a）和Umpc3Um（慢速）（8b）的绝对构型。分别使用亚磷酰胺结构单元11a和11b合成了掺入8a和8b的寡核苷酸U4[Umpc3Um（快速）]U4（13a）和U4[Umpc3Um（慢速）]U4（13b）。这些修饰寡聚物与互补寡聚物形成的双链体的熔解温度实验表明，具有Umpc3Um（快速）的修饰寡聚物13a在手性磷酰基处具有Sp构型。
