硝酸酯 Anomeric Trichloroacetimidates 的单锅微波辅助转化
Summary
一个 2-叠-1-硝酸酯可以转换为相应的 2-叠-1-trichloroacetimidate 在一个锅的程序。该手稿的目的是演示微波反应器在碳水化合物合成中的效用。
Abstract
以下过程的目标是提供一个 2-叠-1-硝酸酯的一锅转换的示范对 trichloroacetimidate 糖捐赠者。经叠硝化后的 glycal, 产品 2-叠-1-硝酸酯可以在微波辅助照射下水解。这种转变通常是通过强亲核试剂和延长反应时间来实现的。微波辐照诱导水解, 在没有试剂的情况下, 反应时间短。在脱硝后, 中间 anomeric 醇在同一锅中转化为相应的 2-叠-1-trichloroacetimidate。
Introduction
由于它们在分子生物学中无处不在, 碳水化合物一直是化学合成的长期目标。1,2,3在任何成功的合成运动的核心是正确部署糖基化反应, 以建立低聚糖链。4,5,6,7,8,9,10,11,12不奇怪的是, 有大量的方法来安装糖苷债券。13,14汤姆·柯尼希斯-克诺尔方法是已知最早的程序之一, 它涉及将糖氯化物或溴化物与酒精成分结合, 通常在重金属 (汞或银) 活化作用下。15相关的糖氟化物在1981年被醛集团首次作为捐赠者引入, 并因其热化学稳定性的提高而得到广泛应用。在反应谱的相反端的16是糖化, 它比其他卤化物的反应要多得多。增加的反应性伴随着增加的 stereocontrol, 特别是当形成α连接的寡糖。17除了 “haloglycosides” 外, thioglycosides 还发现了广泛的效用, 部分原因在于它们易于形成, 稳定性对大量的反应条件和活化亲试剂。18
上述方法的重点是将 anomeric 醇转化为 “氧”, 即由受体分子中的酒精激活并最终取代的潜离组。Anomeric 氧活化, 如施密特学派所描述的, 重点是将 C1 氧本身转化为一个离群。19这种方法是最强大的, 广泛应用于化学糖基化反应。Trichloroacetimidate 捐赠者从还原糖和乙容易地准备, 在基地存在例如碳酸钾 (K2CO3) 或 18-环 [5.4. 0] undec-7-烯 (DBU)。这些物种, 然后激活使用刘易斯酸。20
最近, 我们报告说, 2-叠-1-trichloroacetimidate 捐助者可以直接从 glycals 的准备。这一过程涉及两个反应, 一锅程序从 2-叠-1-硝酸酯。21此详细的协议旨在帮助从业者成功完成高产转化。特别感兴趣的是该序列的第一步, 它着重于微波辅助加热下的热脱硝。我们也希望提供一个直观的教程, 在有机合成中使用微波反应器。
Protocol
Representative Results
Discussion
本教程中描述的协议提供了一种将硝酸酯转化为有用的、无功功能的方法。从更广泛的意义上说, 使用微波反应器来完成碳水化合物合成过程中的特定动作, 有可能使困难的转变变得轻便和例行。在本教程中, 我们的目标是演示如何在微波照射的情况下处理碳水化合物。
在父母反应的情况下, 以前的努力, 以实现脱硝通常依赖于强亲核试剂和延长反应时间。本文所描述的技术的?…
Divulgations
The authors have nothing to disclose.
Acknowledgements
作者要感谢范德比尔特大学和化学生物学研究所的资助。Mr. 伯克利埃利斯和 Prof. 是公认的高分辨率质谱分析。
Materials
| 230 400 mesh silica gel | SiliCycle Inc | R10030B | |
| TLC plates | SiliCycle Inc | TLG-R10014B-527 | |
| Ceric ammonium molybdate | Sigma-Aldrich | A1343 | |
| Solvent Still | Mbraun | MB-SPS-800 | |
| Infared spectrometer | Thermo | Thermo Electron IR100 | |
| Nuclear Magnetic Resonance | Bruker | 400, 600 MHz | |
| LC/MS | Thermo/Dionex | Single quad, ESI | |
| HRMS | Agilent | Synapt G2 S HDMS | |
| Microwave reactor | Anton Parr | Anton Parr G10 Monowave 200 | |
| DBU | Sigma-Aldrich | 139009 | |
| CCl3CN | Sigma-Aldrich | T53805 | |
| Pyridine | Sigma-Aldrich | 270970 | |
| Acetone | Fisher Scientific | A18-20 | Tech. grade |
| Phase separator | Biotage | 120-1901-A | |
| Rotary evaporator | Buchi | R-100 |
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