One-Pot Formation of Large Macrocycles with Modifiable Peripheries and Internal Cavities
One-Pot Formation of Large Macrocycles with Modifiable Peripheries and Internal Cavities
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具有可修饰外围和内部空腔的大环化合物的一锅法形成
DOI：
10.1002/anie.200900584
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发表时间：
2009-01-01
影响因子：
16.6
通讯作者：
Gong, Bing
中科院分区：
文献类型：
--
作者：
Ferguson, Joseph S.;yamato, Kazuhiro;Gong, Bing
由于其独特的性能和潜在的应用前景，具有持久形状和大的、不可折叠的流明的大周期材料越来越受到人们的关注虽然大多数形状明确的大环具有由spor sp2杂化碳原子逐步耦合形成的烃骨架，但也有报道[1a， b, d， 2]具有其他刚性骨架的大环例如，我们发现了一系列芳族低聚酰胺大环，它们可以通过一锅大环化工艺以高收率生成这些容易获得的大环含有富含羰基氧原子的亲水腔。由于具有持久的形状和不可折叠的腔体，这些大环具有独特的特征，如高亲和力和特异性结合大阳离子，[5]和自组装成高导电性的跨膜孔最新的机制研究[4b]表明，未环化的低聚酰胺中间体和前体的折叠在观察到的一锅大环化的高效率中起着关键作用，它们属于一类具有明确的新月形构象和带状骨架的折叠低聚酰胺，[7]。中间体和前体的折叠促进了一锅环化，同时通过远程位阻阻碍了比大环的直接前体更长的“过冲”低聚物的形成。[4b]本文中，我们报道了除芳香低聚酰胺外的骨架大环也可以以非常高的效率形成。具体来说，具有刚性寡肼骨架和纳米级空腔的大环几乎可以在一步中获得，这些空腔含有位置良好、可修改的会聚位点。与我们之前合成的新月形和螺旋形低聚酰胺类似，由间联苯环组成的芳香低聚肼也可以折叠成带状、氢键固化的骨架一般结构1代表了一类未知的芳香族低聚肼，它由间键苯和吡啶残基组成，应该有一个氢键强迫的弯曲主链。1的基本单位由一个氢键合的肼基团组成，两侧是吡啶N和充当氢键受体的醚O原子。这种基本单元的平面构象用优化后的肼1a.[10]结构来说明1a的结构由位于其肼单元两侧的两个非常有利的三中心氢键固化。这些三中心氢键使得1a是平面的。由这种刚性的肼单元和元连接的芳香环组成的低聚物将被迫折叠成新月形，一旦它达到使其两端接近的长度，就可以发生环化。因此，基于1的低聚物应该有一个折叠的，新月形的主链，可以促进大环化，从而导致相应的大环。为了验证这种可能性，在4-二甲氨基吡啶（DMAP）存在下，用CH2Cl2中的肼3（1当量）在08C（方案1）下处理酸氯2（1当量）。将反应混合物加热至室温，回流加热24 h，加入乙醚沉淀粗产物。该产物的MALDI质谱显示一个优势信号（m/z= 1515.0），对应于六残基大环4的[m + Na+]离子。通过柱层析纯化得到纯4为淡黄色固体，收率为73%。4的1H和13C核磁共振谱也显示了…
Macrocycles with persistent shape and large, noncollapsible lumens have attracted increasing interest because of their unique properties and potential applications.[1] Although most of the macrocycles with well-defined shape have hydrocarbon backbones formed from the stepwise coupling of spor sp2-hybridized carbon atoms,[1a, b, d, 2] macrocycles with other rigid backbones have also been reported.[3] For example, we discovered a series of aromatic oligoamide macrocycles that could be generated in high yield by a one-pot macrocyclization process.[4] These readily available macrocycles contain hydrophilic cavities that are rich in carbonyl oxygen atoms. With their persistent shape and noncollapsible cavities, these macrocycles have demonstrated unique features such as binding large cations with high affinity and specificity,[5] and self-assembling into highly conducting transmembrane pores.[6] The latest mechanistic study [4b] indicates that the folding of uncyclized oligoamide intermediates and precursors, which belong to a class of folding oligoamides with welldefined crescent conformations and tapelike backbones,[7] plays a critical role in the observed high efficiency of the one-pot macrocyclization. The folding of the intermediates and precursors facilitates the one-pot cyclization,[8] and at the same time impedes the formation of “overshooting” oligomers longer than the direct precursor of a macrocycle through remote steric hindrance.[4b] Herein we report that macrocycles with backbones other than aromatic oligoamides can also be formed with very high efficiency. Specifically, macrocycles with rigidified oligohydrazide backbones and nanosized cavities containing well-positioned, modifiable convergent sites can be obtained nearly exclusively in one step. Similar to the crescent and helical oligoamides we had previously synthesized, the aromatic oligohydrazides consisting of meta-linked benzene rings are also known to fold into conformations with tapelike, hydrogen-bond-rigidified backbones.[9] General structure 1 represents an unknown class of aromatic oligohydrazides consisting of meta-linked benzene and pyridine residues that should have a hydrogen-bondenforced, curved backbone. The basic unit of 1 consists of a hydrogen-bonded hydrazide group flanked by pyridyl N and ether O atoms that act as hydrogen-bond acceptors. The planar conformation of such a basic unit is illustrated by the optimized structure of hydrazide 1a.[10] The structure of 1a is rigidified by two highly favorable, three-center hydrogen bonds that are placed on either side of its hydrazide unit. These three-center hydrogen bonds enforce 1a to be planar. An oligomer consisting of such rigidified hydrazide units and meta-linked aromatic rings will be forced to fold into a crescent shape, which will allow cyclization to occur once it reaches a length that brings its two ends into proximity. Thus, oligomers based on 1 should have a folded, crescent-shaped backbone that may facilitate macrocyclization, thus leading to the corresponding macrocycle.To test this possibility, acid chloride 2 (1 equiv) was treated with hydrazide 3 (1 equiv) in CH2Cl2 in the presence of 4-dimethylaminopyridine (DMAP) at 08C (Scheme 1). The reaction mixture was allowed to warm to room temperature, and was then heated under reflux for 24 h. The crude product was precipitated by adding diethyl ether. The MALDI mass spectrum of this product revealed a dominant signal (m/z= 1515.0) that corresponded to the [M+ Na+] ion of the six-residue macrocycle 4. Purification by column chromatography gave pure 4 as a pale yellow solid in 73% yield. The 1H and 13C NMR spectra of 4 also revealed …