全合成揭示了小分子天然产物 tryptorubin A 中的非典型对映异构现象。
Total synthesis reveals atypical atropisomerism in a small-molecule natural product, tryptorubin A.
机构信息
Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
出版信息
Science. 2020 Jan 24;367(6476):458-463. doi: 10.1126/science.aay9981. Epub 2020 Jan 2.
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.
分子形状在生物和材料环境中都决定了其功能，化学家们已经开发出越来越多的专业术语来描述这些形状。非经典的对映异构体——形状定义的分子，在形式上拓扑简单，但只能通过复杂的、非物理的多键扭转来相互转化——形成了对映异构体的一个独特子集，与经典的对映异构体（如联萘酚）和拓扑异构体（即具有相同连接性但不同分子图的分子）不同。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。通过全合成，我们发现肽类生物碱 tryptorubin A 可以是两种非经典对映异构体之一。然后，我们设计了一种合成策略，驱动非经典对映定义的小分子的atropospecific 合成。
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