The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA.
Department of Chemistry, The Scripps Research Institute, La Jolla, California, USA.
Nat Protoc. 2016 Aug;11(8):1371-87. doi: 10.1038/nprot.2016.078. Epub 2016 Jul 7.
Cavitands are established tools of supramolecular chemistry and molecular recognition, and they are finding increasing application in sensing and sequestration of physiologically relevant molecules in aqueous solution. The synthesis of a water-soluble, deep cavitand is described. The route comprises six (linear) steps from commercially available precursors, and it relies on the fourfold oligomeric cyclization reaction of resorcinol with 2,3-dihydrofuran that leads to the formation of a shallow resorcinarene framework; condensation with aromatic panels, which deepens the hydrophobic binding cavity; construction of rigid urea functionalities on the upper rim; and the introduction of the water-solubilizing methylimidazolium groups on the lower rim. Late intermediates of the synthesis can be used in the preparation of congener cavitands with different properties and applications, and a sample of such a synthetic procedure is included in this protocol. Emphasis is placed on scaled-up reactions and on purification procedures that afford materials in high yield and avoid chromatographic purification. This protocol provides improvements over previously described procedures, and it enables the preparation of sizable amounts of deep cavitands: 7 g of a water-soluble cavitand can be prepared from resorcinol in 13 working days.
穴醚是超分子化学和分子识别的成熟工具，并且在水溶液中生理相关分子的传感和捕获方面的应用日益广泛。本文描述了一种水溶性的深穴醚的合成方法。该路线由商业可得的前体经过六（线性）步反应得到，依赖于间苯二酚与 2,3-二氢呋喃的四聚环化反应，生成浅的杯[4]芳烃骨架；与芳族嵌段缩合，加深疏水性结合腔；在上边缘构建刚性脲官能团；在下边缘引入水溶性的甲基咪唑基团。合成过程中的晚期中间体可用于制备具有不同性质和应用的同系物穴醚，本方案中包含了这种合成方法的一个示例。重点介绍放大反应和纯化程序，以高产率提供材料并避免色谱纯化。该方案对以前描述的程序进行了改进，使大量深穴醚的制备成为可能：可在 13 个工作日内从间苯二酚制备 7 克水溶性穴醚。
