A trefoil knot made of amino acids and steroids
A trefoil knot made of amino acids and steroids
复制标题
DOI：
10.1002/anie.200601111
复制
发表时间：
2006-01-01
影响因子：
16.6
通讯作者：
Frohlich, Roland
中科院分区：
文献类型：
--
作者：
Feigel, Martin;Ladberg, Rudiger;Frohlich, Roland
5的核磁共振氢谱与4的完全不同(图1)。观察到5的6个Valine-氨基胆酸单元中的每个质子都有两个分辨良好的信号。这两组信号在图1中表示为A和B。在每个Valine-氨基胆酸单元内的质子之间的ROESY谱中没有发现交叉峰，但在A型Valine质子和B型Valine质子之间也观察到了一些NOE接触。[5]显然，A和B类型的valine单元接近，这只有当大环环中这些位置存在收缩或交叉时才可能。大环6也有类似的光谱和NOE数据，它包含苯丙氨酸而不是缬氨酸作为天然氨基酸；该化合物也是按照方案1中概述的路线合成的。[6]在更极性的溶剂(如DMF)和高温(323K)中，5和6中的核磁共振信号持续分裂。因此，氢键本身不太可能是观察到的信号分裂的原因，并假设了5的纽结结构，但不能用核磁共振光谱来证明。分析清楚地表明5具有三叶结的结构(方案2，图2)。[8]该结几乎具有C3对称性。它由三个外部类固醇单元组成的三个等效环路，一个由Valine氨基酸组成的链交叉区，以及一个由三个内部类固醇单元组成的核心。
The 1H NMR spectrum of 5 is completely different from that of 4 (Figure 1). Two well-resolved signals are observed for each proton of the six valine-aminocholanic units of 5. The two sets of signals are denoted as A and B in Figure 1. NOE cross-peaks are found in the ROESY spectra between protons within each valine-aminocholanic acid unit, but some NOE contacts are also observed between valine protons of type A and valine protons of type B.[5] Clearly, the valine units of type A and B come into proximity, which is only possible if there is a constriction or crossing at these sites in the macrocyclic ring. Similar spectra and NOE data are found for macrocycle 6, which contains phenylalanine instead of valine as the natural amino acid; the compound has also been synthesized by the route outlined in Scheme 1.[6] The splitting of the NMR signals in 5 and 6 persists in more-polar solvents (eg DMF) and at elevated temperatures (323K). It is therefore unlikely that hydrogen bonds alone are the reason for the observed splitting of the signals, and a knot structure of 5 was postulated but could not be proved by NMR spectroscopy.[7]Crystals of 5 suitable for X-ray structure determination were grown from n-propanol. The analysis shows unambiguously that 5 has the structure of a trefoil knot (Scheme 2, Figure 2).[8] The knot has almost C3 symmetry. It consists of three equivalent loops made from three external steroid units, a chain-crossing region composed of valine amino acids, and a core built from three internal steroids.