Hindered rotation in arylnaphthalene lignans
Hindered rotation in arylnaphthalene lignans
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DOI：
10.1021/jo952048e
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发表时间：
1996-05-17
影响因子：
3.6
通讯作者：
Chee, GL
中科院分区：
文献类型：
--
作者：
Charlton, JL;Oleschuk, CJ;Chee, GL
许多芳基萘木脂素显示出生物活性，尽管它们中很少含有立体中心，但如果芳基萘键的旋转受到阻碍，它们仍然可能是手性的。相对较高的旋转屏障可能产生可分离的旋转对映体（atropisomer），它们可能具有完全不同的药理学性质。为了探讨这种可能性，我们合成了天然产物正义素A、正义素B、反helioxanthin、反正义素B、helioxanthin以及其他四种芳基萘木脂素类似物。我们用动态NMR和HPLC研究了这些化合物中的芳基-萘旋转势垒，发现旋转势垒的范围在16.9 ~ 21.5 kcal/mol之间。这意味着，在室温下，单个atropisomer的半衰期小于10分钟。实验发现的势垒与分子轨道计算得到的势垒进行了比较。
Many arylnaphthalene lignans show biological activity and although few of them contain stereogenic centers, they may nevertheless be chiral if there is hindered rotation about the aryl-naphthalene bond. A relatively high barrier to rotation may give rise to separable rotational enantiomers (atropisomers) which might have quite different pharmacological properties. In order to investigate this possibility we have synthesized the natural products justicidin A, justicidin B, retro-helioxanthin, retro-justicidin B, and helioxanthin as well as four other arylnaphthalenes lignan analogs. We have studied the aryl-naphthalene rotational barrier in these compounds by dynamic NMR and HPLC and find barriers to rotation ranging from 16.9 to 21.5 kcal/mol. This translates to half-lives for individual atropisomers of less than 10 min at room temperature. The experimentally found barriers are compared to those obtained from molecular orbital calculations.