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。 The L-pentofuranose derivatives (Ⅳa) and D-pentafuran (Ⅳa) were obtained by L-ribose (Ⅲa) and D-ribose (Ⅲb) Sugar derivatives (Ⅳb), and then with 3-hydroxypyrazine-2-carboxamide Vorbruggen coupling, and then through the ring closure, demethanesulfonyl, debenzylation and other synthesized two different configurations of the locked nucleic acid monomer 1- Hydroxymethyl-3 [4- (3-oxopyrazine-2-carboxamido) -7-hydroxy-2,5-dioxabicyclo [2.2.1] heptane (IIa, IIb) Rates were as high as 24.6% and 31.5% respectively. The reaction conditions of the ring closure, the removal of the methanesulfonyl group and the removal of the benzyl group were optimized. The yield of the reaction was 83.5%, 62.5% and 86.9% respectively. The structure of the target product was confirmed by IR, 1H-NMR, MS and elemental analysis.