不同构型的2'-O,4'-C-亚甲基桥双环核苷(锁核酸单体)的合成  

Synthesis of 2'-O,4'-C-Methylene-linked Bicyclic Ribonucleosides(LNA monomers) with Different Configurations

作　　者：高晶晶[1] 罗先金[1] 

机构地区：[1]上海交通大学化学化工学院,上海200240

出　　处：《精细化工》2014年第11期1380-1384,共5页Fine Chemicals

摘　　要：分别以L-核糖(Ⅲa)和D-核糖(Ⅲb)为原料,经过甲磺酰基化、脱异丙叉保护基、乙酰基化得到L-五呋喃糖衍生物(Ⅳa)和D-五呋喃糖衍生物(Ⅳb),然后分别与3-羟基吡嗪-2-酰胺进行Vorbruggen偶合,再经过闭环、脱甲磺酰基、脱苄基等合成了两种不同构型的锁核酸单体1-羟甲基-3[4-(3-氧代吡嗪-2-酰胺)基]-7-羟基-2,5-二氧二环[2.2.1]庚烷(Ⅱa,Ⅱb),总收率分别高达24.6%,31.5%。对闭环、脱除甲磺酰基以及脱除苄基等步骤的反应条件进行了优化,收率分别达到83.5%,62.5%,86.9%。目标产物的结构经过红外光谱、核磁共振氢谱、质谱、元素分析进行确证。L-pentofuranose derivative（4a） and D-pentofuranose derivative（4b） were synthesized via mesylation, removing isopropylidene group and acetylation with L-ribofuranose （3a） and D-ribofuranose（（3b） as starting materials, respectively. Subsequent Vorbruggen coupling with 3-oxo-5,6-dihydropyrazine-2-carboxamide, cyclization, demesylation and debenzylation afforded 7-Hydroxy-1-（hydroxymethyl）-3-[4-（3-oxo-3,4-dihydropyrazine-2-carboxamide）-yl]-2,5-dioxabicyclo[2.2.1] heptane with two different configurations （2a, 2b） in yields 24.6% and 31.5% , respectively. The reaction conditions of ring-closing, demesylation and debenzylation were optimized with yields 83.5%, 62.5% and 86.9%. The chemical structures of target compounds were finely identified by IR, 1H NMR, MS and elementary analysis.

关 键 词：锁核酸 呋喃糖 核苷 吡嗪酰胺 医药与日化原料 

分 类 号：R978.7[医药卫生—药品] R979.1[医药卫生—药学]