A twisted small-molecule synthesis Some molecules are easy to draw on paper, whereas others contain rings and contortions that require one to think in three dimensions. Reisberg et al. set out to synthesize the bicyclic small molecule tryptorubin A but found that their initial attempt produced a molecule with the right bonds but the wrong molecular shape, a form of noncanonical atropisomerism. The authors then devised a synthesis where they locked in the correct isomer before forming the second ring, which produced a product indistinguishable from the authentic natural product. Such structural isomers may be lurking when working with complex small molecules with constrained rotation. Science, this issue p. 458 A complex small molecule can be synthesized in two, noninterconvertible conformations. Molecular shape defines function in both biological and material settings, and chemists have developed an ever-increasing vernacular to describe these shapes. Noncanonical atropisomers—shape-defined molecules that are formally topologically trivial but are interconvertible only by complex, nonphysical multibond torsions—form a unique subset of atropisomers that differ from both canonical atropisomers (e.g., binaphthyls) and topoisomers (i.e., molecules that have identical connectivity but nonidentical molecular graphs). Small molecules, in contrast to biomacromolecules, are not expected to exhibit such ambiguous shapes. Using total synthesis, we found that the peptidic alkaloid tryptorubin A can be one of two noncanonical atropisomers. We then devised a synthetic strategy that drives the atropospecific synthesis of a noncanonical atrop-defined small molecule.

中文翻译：

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全合成揭示了小分子天然产物色氨酸 A 中的非典型阻转异构现象

一种扭曲的小分子合成 有些分子很容易在纸上画出来，而另一些分子则包含需要从三个维度进行思考的环和扭曲。赖斯伯格等人。开始合成双环小分子色氨酸 A，但发现他们最初的尝试产生了一种具有正确键但分子形状错误的分子，这是一种非规范的阻转异构现象。然后，作者设计了一种合成方法，在形成第二个环之前锁定正确的异构体，从而产生与真正的天然产品无法区分的产品。当处理旋转受限的复杂小分子时，这种结构异构体可能潜伏着。科学，这个问题 p。458 一个复杂的小分子可以合成为两种不可相互转换的构象。分子形状定义了生物和材料环境中的功能，化学家开发了一种不断增加的术语来描述这些形状。非典型阻转异构体——形状定义的分子，在形式上是拓扑微不足道的，但只能通过复杂的、非物理的多键扭转才能相互转化——形成独特的阻转异构体子集，它们不同于典型的阻转异构体（例如联萘）和拓扑异构体（即具有相同连接性的分子）但不同的分子图）。与生物大分子相比，小分子预计不会表现出如此模糊的形状。使用全合成，我们发现肽类生物碱色氨酸 A 可以是两种非经典阻转异构体之一。