Kusakabe Kazuaki, Honmura Yuna, Uesugi Shota, Tonouchi Akio, Maeda Hayato, Kimura Ken-Ichi, Koshino Hiroyuki, Hashimoto Masaru
Faculty of Agriculture and Life Science, Hirosaki University , 3-Bunkyo-cho, Hirosaki, 036-8561, Japan.
The United Graduate School of Agricultural Sciences, Iwate University , Morioka, 020-8550, Japan.
J Nat Prod. 2017 May 26;80(5):1484-1492. doi: 10.1021/acs.jnatprod.6b01177. Epub 2017 Apr 26.
Neomacrophorin X (1) was isolated from Trichoderma sp. 1212-03. Heteronuclear multiple bond correlation (HMBC) spectral analysis indicated a unique [4.4.3]propellane framework, which was verified by the H and C chemical shift calculations based on density functional theory (DFT) and subsequent comparison with experimental data obtained in CDCl. The DFT-based electronic circular dichroism (ECD) calculations were effective in not only determining the absolute configuration but also confirming the relative structure. The predominant conformation of 1 was found to be solvent-dependent, with different conformations presenting different NMR and ECD profiles. Introduction of J-based analysis with a J-resolved HMBC aided in this investigation. This conformational alternation was reproduced by considering the solvation with the SM5.4 model in the calculation, although it was not sufficiently quantitative. Although the calculations without solvent effects suggested a conformer that satisfies the spectral profiles in CDCl, postcalculations with the SM5.4 solvation protocol stabilized the second major conformer, which reproduces the NMR and ECD profiles in polar solvents. Neomacrophorin X (1) is assumed to be biosynthesized by a coupling between the reduced form of anthraquinone and a neomacrophorin derivative. This hypothesis was supported experimentally by the isolation of pachybasin and chrysophanol, as well as acyclic premacrophorin (2), from the same fungus. Some biological properties of 1 are described.
新巨噬蛋白X（1）是从木霉菌1212 - 03中分离得到的。异核多键相关（HMBC）光谱分析表明其具有独特的[4.4.3]螺旋烷骨架，基于密度泛函理论（DFT）的H和C化学位移计算以及随后与在CDCl中获得的实验数据进行比较，证实了该骨架。基于DFT的电子圆二色性（ECD）计算不仅有效地确定了绝对构型，还证实了相对结构。发现1的主要构象依赖于溶剂，不同的构象呈现出不同的NMR和ECD谱。引入基于J的分析以及J分辨HMBC有助于此项研究。通过在计算中考虑使用SM5.4模型进行溶剂化作用，再现了这种构象变化，尽管其定量程度不足。尽管不考虑溶剂效应的计算表明存在一种符合CDCl中光谱特征的构象异构体，但使用SM5.4溶剂化协议进行的后计算使第二种主要构象异构体稳定下来，该构象异构体再现了极性溶剂中的NMR和ECD谱。新巨噬蛋白X（1）被认为是由蒽醌的还原形式与新巨噬蛋白衍生物偶联生物合成的。从同一真菌中分离出帕西巴辛、大黄酚以及无环前巨噬蛋白（2），从实验上支持了这一假设。文中描述了1的一些生物学特性。
