Synthesis and Properties of 4′-ThioLNA/BNA
Synthesis and Properties of 4′-ThioLNA/BNA
复制标题
4′-ThioLNA/BNA的合成及性能
DOI：
10.1021/acs.orglett.1c01306
复制
发表时间：
2021
期刊：
影响因子：
5.2
通讯作者：
Yoshimura Yuichi
中科院分区：
文献类型：
--
作者：
Maeda Rion;Saito-Tarashima Noriko;Wakamatsu Hideaki;Natori Yoshihiro;Minakawa Noriaki;Yoshimura Yuichi
为了开发适用于寡核苷酸治疗的新核苷类似物，我们设计了LNA/BNA单体的4′-硫代类似物。以5-硫代吡喃糖衍生物为原料，通过缩环羟醛缩合反应和相应亚砜的Pummerer型巯基糖基化反应合成了4′-羟甲基-4 ′-硫代核糖核苷。以碳酸二苯酯为催化剂，NaHCO 3为催化剂，将4′-羟甲基-4 ′-硫代嘧啶核苷与碳酸二苯酯反应，得到4′-硫代LNA/BNA单体，并将其引入寡核苷酸中。
To develop a new nucleoside analogue applicable to oligonucleotide therapeutics, we designed a 4′-thio analogue of an LNA/BNA monomer. Synthesis of 4′-hydroxymethyl-4′-thioribonucleoside was achieved by a tandem ring-contraction-aldol reaction of a 5-thiopyranose derivative and the subsequent Pummerer-type thioglycosylation reaction of the corresponding sulfoxide. Treatment of 4′-hydroxymethyl-4′-thiopyrimidine nucleosides with diphenyl carbonate in the presence of catalytic NaHCO3gave the desired 4′-thioLNA/BNA monomers, which were introduced into oligonucleotides.