Synthesis of tetradialdose phosphonate nucleosides as mimics of L-nucleotides
Synthesis of tetradialdose phosphonate nucleosides as mimics of L-nucleotides
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DOI：
10.1016/j.tet.2019.130497
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发表时间：
2019-09-13
期刊：
影响因子：
2.1
通讯作者：
Herdewijn, Piet
中科院分区：
文献类型：
--
作者：
Li, Qingfeng;Groaz, Elisabetta;Herdewijn, Piet
结构修饰的核苷类似物是用于掺入能够干扰信息传递或其他生物功能的合成寡核苷酸的治疗剂和结构单元的主要来源。本工作描述了含两个异头中心的非天然L-核苷膦酸酯模拟物的合成。这些化合物的特征是二羟基或单羟基四醛糖作为糖基单位，而腺嘌呤作为核碱基存在。通过在商业1-O-乙酰基-2，3，5-三-O-苯甲酰基-β-D-呋喃核糖的2-和3-位上明智地使用保护基，膦酸酯和核碱基部分都被立体选择性地引入，以提供具有顺式构型取代基的二羟基化化合物作为唯一的反应产物。随后在3 '-位顺利进行选择性脱保护和脱氧，得到相应的含有4'-单羟基四二醛酮的类似物。(C)2019爱思唯尔有限公司版权所有。
Structurally modified nucleoside analogues are a major source of therapeutic agents and building blocks for incorporation into synthetic oligonucleotides able to interfere with information transfer or other biological functions. This work describes the synthesis of non-natural L-nucleoside phosphonate mimics containing two anomeric centers. Such compounds feature either a di- or monohydroxy tetradialdose sugar as the glycone unit, while adenine is present as nucleobase. By judicious use of protecting groups at the 2- and 3-position of commercial 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribofuranose, both the phosphonate and nucleobase moieties were stereoselectively introduced to provide a dihydroxylated compound with cis-configured substituents as the sole reaction product. Subsequent selective deprotection and deoxygenation at the 3'-position occurred smoothly to afford the corresponding 4'-monohydroxy tetradialdose containing analogue. (C) 2019 Elsevier Ltd. All rights reserved.