A new generation of ''cholaphanes'': Steroid-derived macrocyclic hosts with enhanced solubility and controlled flexibility
A new generation of ''cholaphanes'': Steroid-derived macrocyclic hosts with enhanced solubility and controlled flexibility
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DOI：
10.1021/jo971272w
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发表时间：
1997-11-28
影响因子：
3.6
通讯作者：
Williams, DJ
中科院分区：
文献类型：
--
作者：
Bhattarai, KM;Davis, AP;Williams, DJ
以价格低廉的甾体胆酸为原料合成了大环“胆碱”3a-c。像早期的亲戚一样，它们具有向内导向羟基的大量空腔，适合在非极性介质中结合极性分子，如碳水化合物。新的特征是外定向烷基链，提高了有机溶剂中的溶解度，并且（在3b/c的情况下）由于甾体侧链的截断而降低了构象自由度。特别地，建模表明最小的大环3c具有很小的柔韧性，倾向于开放构象，这也显示在其五水合物的x射线晶体结构中。核磁共振研究表明，这三种胆碱在CDCl3中与辛基β - d -葡萄糖苷形成1:1的配合物，K-a = 600-1560 M-1。证明了Cholaphanes 3b/c能够从水溶液中提取甲基β - d -葡萄糖苷到CHCl3中。甲基β - d -葡萄糖苷通过氯仿屏障的运输也被证明为3c。
The macrocyclic ''cholaphanes'' 3a-c were synthesized from the inexpensive steroid cholic acid. Like earlier relatives they feature substantial cavities with inward-directed hydroxyl groups, suitable for binding polar molecules such as carbohydrates in nonpolar media. New features are the externally directed alkyl chains, promoting solubility in organic solvents, and (in the case of 3b/c) reduced conformational freedom resulting from truncation of the steroidal side-chain. In particular, modeling shows that the smallest macrocycle 3c possesses very little flexibility, preferring an open conformation which is also revealed in the X-ray crystal structure ofits pentahydrate. NMR studies indicated that all three cholaphanes form 1:1 complexes with octyl beta-D-glucoside in CDCl3, with K-a = 600-1560 M-1. Cholaphanes 3b/c proved able to extract methyl beta-D-glucoside from aqueous solutions into CHCl3. The transport of methyl beta-D-glucoside across a chloroform barrier was also demonstrated for 3c.