Bracher Franz, Eisenreich Wolfram J, Mühlbacher Jörg, Dreyer Michael, Bringmann Gerhard
Department Pharmazie, Ludwig-Maximilians-Universität, Butenandtstrasse 5-13, D-81377 Münich, Germany.
J Org Chem. 2004 Dec 10;69(25):8602-8. doi: 10.1021/jo048631p.
The first biarylic bis-morphinanedienone alkaloids, saludimerines A (3a) and B (3b), isolated from a tree of Croton flavens (Euphorbiaceae) are described. These naturally occurring dimers of the known alkaloid salutaridine are joined together via a rotationally hindered biaryl axis, giving rise to atropo-diastereomers that are configurationally stable at room temperature but slowly interconvert in methanolic solution within several days. Their structures were established by spectroscopic methods and by partial synthesis, which was achieved by a highly atropo-diastereoselective biomimetic oxidative coupling of the monomeric precursor, salutaridine. Their axial configurations were elucidated by circular dichroism (CD) investigations, which succeeded despite the fact that the two atropo-diastereomers exhibit near-identical CD spectra. This remarkable phenomenon was rationalized by quantum chemical CD calculations. The configurational assignment of saludimerines A (3a) as P-axial and B (3b) as M was corroborated by atropisomer-specific NOE interactions between protons of the one molecular half with nuclei in the other.
本文描述了从巴豆属植物黄巴豆（大戟科）中分离得到的首例联芳基双吗啡烷二烯酮生物碱——黄巴豆碱A（3a）和B（3b）。这些已知生物碱水苏替丁的天然二聚体通过受阻旋转的联芳基轴连接在一起，形成了阻转非对映异构体，它们在室温下构型稳定，但在甲醇溶液中数天内会缓慢相互转化。通过光谱方法和部分合成确定了它们的结构，部分合成是通过单体前体水苏替丁的高度阻转非对映选择性仿生氧化偶联实现的。通过圆二色性（CD）研究阐明了它们的轴向构型，尽管这两种阻转非对映异构体的CD光谱几乎相同，但研究仍取得了成功。这种显著现象通过量子化学CD计算得到了合理解释。通过一个分子半部分的质子与另一个分子中的原子核之间的阻转异构体特异性NOE相互作用，证实了黄巴豆碱A（3a）的构型为P-轴向，B（3b）的构型为M-轴向。
