美国斯克里普斯研究所Phil S. Baran、哈佛医学院Jon Clardy等研究人员合作利用全合成揭示小分子天然产物tryptorubin A中的非典型位阻异构。相关论文于2020年1月2日在线发表在《科学》上。

研究人员通过全合成发现肽生物碱tryptorubin A可以是两种非经典阻转异构体之一。随后，研究人员设计了一种合成策略，其可实现非经典小分子的首次位阻异构合成。

据介绍，分子形状定义了生物学和材料环境中的功能，因此，化学家已经开发出越来越多的描述性通俗词汇来描述这些形状。非经典的阻转异构体（即形状定义的分子，其拓扑上微不足道但只能通过复杂的、非物理的多键扭转互变）形成了独特的阻转异构体子集，不同于规范的阻转异构体（例如，双萘基）和拓扑异构体（即具有相同连通性但分子图不同的分子）。与生物大分子相反，小分子不会表现出这种模棱两可的形状。

附：英文原文

Title: Total synthesis reveals atypical atropisomerism in a small-molecule natural product, tryptorubin A

Author: Solomon H. Reisberg, Yang Gao, Allison S. Walker, Eric J. N. Helfrich, Jon Clardy, Phil S. Baran

Issue&Volume: 2020/01/02

Abstract: Molecular shape defines function in both biological and material settings and, as such, chemists have developed an ever-increasing descriptive vernacular to describe these shapes. Non-canonical atropisomers—i.e., shape-defined molecules that are formally topologically trivial, but only interconvertible by complex, non-physical 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 non-identical molecular graphs). Small molecules, in contrast to biomacromolecules, are not expected to exhibit such ambiguous shapes. Herein, we present the discovery through total synthesis that the peptidic alkaloid tryptorubin A can be one of two non-canonical atropisomers. We subsequently devised a synthetic strategy that drives the first atropospecific synthesis of a non-canonical atrop-defined small molecule.

DOI: 10.1126/science.aay9981

Source: https://science.sciencemag.org/content/early/2019/12/30/science.aay9981