Arreaga-González Héctor M, Oliveros-Ortiz Antonio J, Del Río Rosa E, Rodríguez-García Gabriela, Torres-Valencia J Martín, Cerda-García-Rojas Carlos M, Joseph-Nathan Pedro, Gómez-Hurtado Mario A
Departamento de Química, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado 14-740, Mexico City 07000, Mexico.
Instituto de Investigaciones Químico Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Ciudad Universitaria, Morelia, Michoacán 58030, Mexico.
J Nat Prod. 2021 Mar 26;84(3):707-712. doi: 10.1021/acs.jnatprod.0c01113. Epub 2021 Mar 8.
Since epoxythymols occur in Nature either as scalemic mixtures or as pure enantiomers, the knowledge of their chiral composition and of the absolute configuration (AC) of the dominant enantiomer turns out to be mandatory. This task has already been faced using 1,1-bis-2-naphthol (BINOL), as a chiral solvating agent in accurate H NMR quantifications to determine the enantiomeric ratio, and vibrational circular dichroism (VCD) to evidence the AC of the dominant enantiomer. We now explore the use of electronic circular dichroism (ECD) to determine the AC of an epoxythymol for which time-expensive DFT calculations would be required unless the AC of a related molecule is already known, from either VCD studies or single-crystal X-ray diffraction analysis, since one could correlate the ECD Cotton effect with the AC because in ECD only chromophores and their neighborhoods are evidenced. This method is now applied by using the epoxythymols from . Known areolal () and 10-cinnamoyloxy-8,9-epoxythymol isobutyrate () were isolated from the roots, while known 7-acetoxy-10-cinnamoyloxy-8,9-epoxythymol isobutyrate () and 10-cinnamoyloxy-7-hydroxy-8,9-epoxythymol isobutyrate (), as well as the new enantiopure 7-acetoxy-10-cinnamoyloxy-6-hydroxy-8,9-epoxythymol isobutyrate () and 10-cinnamoyloxy-8,9-epoxy-6-hydroxy-7-thymol isobutyrate (), were obtained from the extract of the flowers. Chemical correlation of epoxythymols and was achieved. Compounds - were obtained as scalemic mixtures, and and as the pure (8) enantiomers. In addition, the new 10-cinnamoyloxy-7-oxo-8,9-dehydrothymol isobutyrate () was isolated from the roots. The structures of - followed from NMR and HRMS data, while enantiomeric compositions of - were determined by H NMR-BINOL measurements. The AC determination for - was done by ECD using a sample of to reference the ECD Cotton effect. In turn, the AC of was determined by VCD and extensive DFT calculations. The ECD-BINOL methodology turned out to be some 500 times more sensitive than that combining VCD and H NMR-BINOL.
由于环氧百里香酚在自然界中以非对映体混合物或纯对映体的形式存在，因此了解它们的手性组成以及主要对映体的绝对构型（AC）变得至关重要。此前已采用1,1-双-2-萘酚（BINOL）作为手性溶剂化剂，通过精确的核磁共振氢谱（H NMR）定量来确定对映体比例，并利用振动圆二色性（VCD）来确定主要对映体的AC，从而解决了这一问题。我们现在探索使用电子圆二色性（ECD）来确定环氧百里香酚的AC，对于这种物质，除非已经通过VCD研究或单晶X射线衍射分析知道相关分子的AC，否则需要进行耗时的密度泛函理论（DFT）计算，因为在ECD中，人们可以将ECD科顿效应与AC相关联，因为在ECD中仅能显示发色团及其周围环境。现在通过使用来自[具体来源未给出]的环氧百里香酚来应用此方法。已知的阿雷洛醇（[具体名称未给出]）和10-肉桂酰氧基-8,9-环氧百里香酚异丁酸酯（[具体名称未给出]）是从根部分离得到的，而已知的7-乙酰氧基-10-肉桂酰氧基-8,9-环氧百里香酚异丁酸酯（[具体名称未给出]）和10-肉桂酰氧基-7-羟基-8,9-环氧百里香酚异丁酸酯（[具体名称未给出]），以及新的对映体纯的7-乙酰氧基-10-肉桂酰氧基-6-羟基-8,9-环氧百里香酚异丁酸酯（[具体名称未给出]）和10-肉桂酰氧基-8,9-环氧-6-羟基-7-百里香酚异丁酸酯（[具体名称未给出]）是从花的提取物中获得的。实现了环氧百里香酚[具体编号未给出]和[具体编号未给出]的化学关联。化合物[具体编号未给出] - [具体编号未给出]以非对映体混合物形式获得，而[具体编号未给出]和[具体编号未给出]以纯（8）对映体形式获得。此外，新的10-肉桂酰氧基-7-氧代-8,9-脱氢百里香酚异丁酸酯（[具体名称未给出]）是从根部分离得到的。[具体编号未给出] - [具体编号未给出]的结构由核磁共振（NMR）和高分辨质谱（HRMS）数据确定，而[具体编号未给出] - [具体编号未给出]的对映体组成通过核磁共振氢谱 - BINOL测量确定。[具体编号未给出] - [具体编号未给出]的AC测定通过ECD进行，使用[具体编号未给出]的样品来参考ECD科顿效应。反过来，[具体编号未给出]的AC通过VCD和广泛的DFT计算确定。结果表明，ECD - BINOL方法比结合VCD和核磁共振氢谱 - BINOL的方法灵敏约500倍。
