| 达清越,崔喆,马慧萍,景临林.化学通报,2023,86(11):1357-1362. |
| 氮氧自由基三氮唑糖苷衍生物的设计、合成、结构表征与抗缺氧活性评价 |
| Design, Synthesis, Characterization and Anti-hypoxia Activity of Conjugates of Nitronyl Nitroxide and N-glycosides Linked by 1,2,3-triazole |
| 投稿时间：2023-04-11 修订日期：2023-04-24 |
| DOI： |
| 中文关键词: 氮氧自由基 1,2,3-三氮唑 糖苷 合成 |
| 英文关键词:Nitronyl nitroxide, 1,2,3-triazole, Glycoside, synthesis |
| 基金项目:国家自然科学基金项目(81872796)和西安交通大学第一附属医院科研发展基金项目(2022MS-11)资助 |
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| 中文摘要: |
| 氮氧自由基HPN作为一种新型的自由基清除剂，具有良好的抗缺氧活性。为了改善HPN的溶解性和抗缺氧活性，本项目根据活性基团拼接原理，合成了一系列糖基化三氮唑HPN衍生物。首先以乙腈为溶剂、碳酸钾为碱，HPN与1-溴丙炔反应将炔丙基引入HPN分子中，然后在CuI/DIPEA催化下和乙酰叠氮糖发生1,3-偶极环加成反应合成乙酰糖基化三氮唑HPN衍生物（2a~2e），最后在CH3ONa/CH3OH条件下脱除乙酰基得到5个糖基化三氮唑HPN衍生物（3a~3e）。化合物3a~3e产率均在80%以上，化学结构经过红外光谱（IR）、电子顺磁共振（EPR）、质谱（MS）和元素分析（EA）确证。通过常压密闭缺氧实验和急性减压耐受实验考察化合物的抗缺氧活性，结果表明：化合物3a~3e均可以延长常压密闭缺氧小鼠的生存时间，降低急性减压小鼠的死亡率。化合物3a~3e合成方法简便，反应条件温和、产率较高，其中化合物3a~3d的水溶性明显增加，同时表现出类似或者优于HPN的抗缺氧活性。 |
| 英文摘要: |
| HPN is a novel free radical scavenger with good anti-hypoxic activity. In order to improve the solubility and anti-hypoxia activity of nitronyl nitroxide HPN, a series of novel conjugates of HPN and N-glycosides linked by 1,2,3-triazole were designed and synthesized by using the principle of active substructure combination. The propargyl group was introduced by the reaction of HPN with propargyl bromidein using K2CO3 as base and acetonitrile as solvent. Next, attachment of N-glycosides to the HPN core was performed by CuI/DIPEA-catalyzed 1,3-dipolar cycloaddition of β-azido-glycosides with propargyl-HPN, which afforded the corresponding 1,2,3-triazoles. Subsequently, the acetyl was removed in CH3ONa/CH3OH, which resulted in five targeted compounds (3a~3e). The yield of target derivatives was above 80% and the structures of the target compounds were confirmed by infrared (IR), electron paramagnetic resonance (EPR), mass spectrometer (MS) and element analysis (EA). The normobaric hypoxia test and AHH test verified that Compounds 3a~3e could prolong the survival time of mice and reduce the mortality of mice. Compounds 3a~3e were synthesized by a simple method with mild reaction conditions and high yields. Among them, compounds 3a~3d showed significantly increased water solubility, but still exhibited anti-hypoxic activity similar to or better than that of HPN. |
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