Department of Organic Chemistry and Macromolecular Chemistry, Heinrich-Heine-University Düsseldorf , 40225 Düsseldorf, Germany.
Department of Chemistry, Davidson College , Davidson, North Carolina 28035, United States.
J Org Chem. 2017 Sep 15;82(18):9400-9409. doi: 10.1021/acs.joc.7b01398. Epub 2017 Sep 7.
The investigation of heteromultivalent interactions of complex glycoligands and proteins is critical for understanding important biological processes and developing carbohydrate-based pharmaceutics. Synthetic glycomimetics, derived by mimicking complex glycoligands on a variety of scaffolds, have become important tools for studying the role of carbohydrates in chemistry and biology. In this paper, we report on a new synthetic strategy for the preparation of monodisperse, sequence-defined glycooligomers or so-called precision glycomacromolecules based on solid phase oligomer synthesis and the Staudinger ligation. This strategy employs a solid-supported synthetic approach using a novel carboxy-functionalized building block which bears a functional handle required for Staudinger ligation on solid support. Furthermore, we combined Staudinger ligation and copper catalyzed azide alkyne cycloaddition (CuAAC) reactions to synthesize heteromultivalent glycooligomers on solid support for the first time, demonstrating the utility of this approach for the synthesis of heterofunctional glycomacromolecules.
研究复杂糖缀合物与蛋白质的异多价相互作用对于理解重要的生物学过程和开发基于碳水化合物的药物至关重要。通过在各种支架上模拟复杂糖缀合物而衍生出的合成糖模拟物已成为研究碳水化合物在化学和生物学中作用的重要工具。在本文中，我们报告了一种新的基于固相寡聚合成和 Staudinger 连接的制备单分散、序列定义的糖齐聚物或所谓的精确糖大分子的合成策略。该策略采用了一种使用新型羧基功能化砌块的固相合成方法，该砌块在固相载体上带有用于 Staudinger 连接的功能手柄。此外，我们首次将 Staudinger 连接和铜催化叠氮-炔烃环加成（CuAAC）反应结合起来，在固相载体上合成异多价糖齐聚物，证明了该方法在合成异官能团糖大分子中的实用性。
