O'Farrell Courtney M, Chudomel J Matthew, Collins Jan M, Dignam Catherine F, Wenzel Thomas J
Department of Chemistry, Bates College, Lewiston, ME 04240, USA.
J Org Chem. 2008 Apr 4;73(7):2843-51. doi: 10.1021/jo702751z. Epub 2008 Mar 13.
Water-soluble calix[4]resorcinarenes containing 3- and 4-hydroxyproline, d-nipecotic acid, (S)-2-(methoxymethyl)pyrrolidine, (S)-2-pyrrolidine methanol, and (S,S)-(+)-2,4-bis(methoxymethyl)pyrrolidine substituents are synthesized and evaluated as chiral NMR solvating agents. The derivatives with the hydroxyproline groups are especially effective at causing enantiomeric discrimination in the spectra of water-soluble cationic and anionic compounds with pyridyl, phenyl, and bicyclic aromatic rings. Binding studies show that mono- and ortho-substituted phenyl rings associate within the cavity of the calix[4]resorcinarenes, as do naphthyl rings with mono-, 2,3-, and 1,8-substitution patterns. Anthracene derivatives with an amino or sulfonyl group at the 1-position bind within the cavity, as well. Aromatic resonances of the substrates exhibit substantial upfield shifts because of shielding from the aromatic rings of the calix[4]resorcinarene. The effectiveness of the reagents at producing chiral recognition in 1H NMR spectra is demonstrated with sodium mandelate, the sodium salt of tryptophan, and doxylamine succinate. While no one reagent is consistently the most effective, the calix[4]resorcinarenes with trans-4-hydroxyproline and trans-3-hydroxyproline moieties generally produce the largest nonequivalence in the 1H NMR spectra of the substrates.
合成了含有3-和4-羟基脯氨酸、d-哌啶酸、(S)-2-(甲氧基甲基)吡咯烷、(S)-2-吡咯烷甲醇以及(S,S)-(+)-2,4-双(甲氧基甲基)吡咯烷取代基的水溶性杯[4]间苯二酚芳烃，并将其作为手性核磁共振溶剂化剂进行评估。带有羟基脯氨酸基团的衍生物在使具有吡啶基、苯基和双环芳环的水溶性阳离子和阴离子化合物的光谱中产生对映体识别方面特别有效。结合研究表明，单取代和邻位取代的苯环在杯[4]间苯二酚芳烃的腔内缔合，萘环以及具有单取代、2,3-和1,8-取代模式的萘环也是如此。在1-位带有氨基或磺酰基的蒽衍生物也在腔内结合。由于杯[4]间苯二酚芳烃的芳环的屏蔽作用，底物的芳族共振显示出明显的高场位移。用扁桃酸钠、色氨酸钠盐和多西拉敏琥珀酸盐证明了这些试剂在1H NMR光谱中产生手性识别的有效性。虽然没有一种试剂始终是最有效的，但带有反式-4-羟基脯氨酸和反式-3-羟基脯氨酸部分的杯[4]间苯二酚芳烃通常在底物的1H NMR光谱中产生最大的不等同。
