Unique solvent-dependent atropisomerism of a novel cytotoxic naphthoxanthene antibiotic FD-594
Unique solvent-dependent atropisomerism of a novel cytotoxic naphthoxanthene antibiotic FD-594
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DOI：
10.1021/jo982182
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发表时间：
1999-07-23
影响因子：
3.6
通讯作者：
Qiao, YF
中科院分区：
文献类型：
--
作者：
Eguchi, T;Kondo, K;Qiao, YF
通过X射线衍射测定了新型细胞毒性抗生素FD-594 1的绝对立体化学，并通过CD和NMR光谱研究了其构象。发现1的苷元部分具有(3R,6S,7S)构型。特别有趣的是 1 和相关化合物的溶剂依赖性阻转异构现象。 1 的 CD 光谱在两种溶剂体系中表现出几乎相反的镜像曲线，具体取决于溶剂。虽然在 CHCl3 中观察到较大的负 Cotton 效应（Delta epsilon = -33.9, 279 nm），但在甲醇中也出现了类似的正 Cotton 效应（Delta epsilon = 38.9, 279 nm），很可能是由于剧烈的构象变化。在苷元 2 和苷元甲基醚 4 中观察到类似的手性反转。这些结果可以用溶剂依赖性阻转异构现象来最好地描述。这是首次观察到天然产物的溶剂依赖性阻转异构现象。基于分子力学计算，讨论了在不同溶剂中扰乱稳定构象的关键因素。
The absolute stereochemistry of FD-594 1, a new cytotoxic antibiotic, was determined by X-ray diffraction, and its conformation was studied by CD and NMR spectroscopy. The aglycon part of 1 was found to have (3R,6S,7S) configuration. Particularly interesting was the solvent-dependent atropisomerism of 1 and related compounds. The CD spectra of 1 exhibited in two solvent systems almost opposite mirror-image curves depending on the solvent. While a large negative Cotton effect (Delta epsilon = -33.9, 279 nm) was observed in CHCl3, a similar positive Cotton effect (Delta epsilon = 38.9, 279 nm) appeared in methanol most probably due to dramatic conformational changes. Similar chiroptical reversal was observed in aglycon 2 and aglycon methyl ether 4. These results can be best described in terms of solvent-dependent atropisomerism. This constitutes the first observation of solvent-dependent atropisomerism of a natural product. The crucial factor that perturbs the stable conformation in different solvents is discussed on the basis of molecular mechanics calculations.