Remodelling of the natural product fumagillol employing a reaction discovery approach.
Remodelling of the natural product fumagillol employing a reaction discovery approach.
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在寻找新的生物活性分子时，面向多样性的合成（DOS）策略通过采样新的化学空间突破了传统文库合成的限制。许多天然产物可被视为 DOS 的有趣起点，其中立体化学丰富的核心结构可以重组为与母体结构明显不同的化学型。理想情况下，此类转换应该是通用的，并且涉及很少的步骤，以便适合图书馆应用程序。考虑到这一目标，高含氧天然产物烟曲霉醇已利用基于反应发现的方法以多种方式成功重塑。在与胺的反应中，通过适当的催化剂与母体分子的尺寸依赖性相互作用，可以在双环氧化物开环/环化序列中获得优异的区域控制，形成全氢异吲哚或全氢异喹啉产物。全氢异吲哚可以通过级联过程进一步重构，以提供吗啉酮或桥联的含 4,1-苯并氮杂卓的结构。
In search for new biologically active molecules, diversity-oriented synthetic (DOS) strategies break through the limitation of traditional library synthesis by sampling new chemical space. Many natural products can be regarded as intriguing starting points for DOS, wherein stereochemically rich core structures may be reorganized into chemotypes which are distinctly different from the parent structure. Ideally such transformations should be general and involve few steps in order to be suited for library applications. With this objective in mind, the highly oxygenated natural product fumagillol has been successfully remodeled in several ways utilizing a reaction discovery-based approach. In reactions with amines, excellent regiocontrol in a bis-epoxide opening/cyclization sequence can be obtained by size-dependent interaction of an appropriate catalyst with the parent molecule, forming either perhydroisoindole or perhydroisoquinoline products. Perhydroisoindoles can be further remodeled by cascade processes to afford either morpholinone or bridged 4,1-benzoxazepine-containing structures.
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影响因子：
4.2
作者：
Frankowski, Kevin J.;Ghosh, Partha;Setola, Vincent;Tran, Thuy B.;Roth, Bryan L.;Aube, Jeffrey
通讯作者：
Aube, Jeffrey
影响因子：
5.2
作者：
Han, Chong;Rangarajan, Sathish;Porco, John A., Jr.
通讯作者：
Porco, John A., Jr.
影响因子：
5.2
作者：
Appendino, G;Tron, GC;Sterner, O
通讯作者：
Sterner, O
影响因子：
7.3
作者：
Franke, Lutz;Schwarz, Oliver;Schneider, Gisbert
通讯作者：
Schneider, Gisbert
影响因子：
3.6
作者：
Krchnak, Viktor;Waring, Katherine R.;Miller, Marvin J.
通讯作者：
Miller, Marvin J.