北京大学Tuoping Luo小组实现了(-)-Zygadenine的对映选择性全合成。这一研究成果于2023年9月8日发表在国际顶尖学术期刊《美国化学会杂志》上。

在该研究中，团队开发了一种新的合成途径以获得Veratrum生物碱这一天然产物家族，这使得(-)-zygadenine的首次全合成成为可能。该合成路线需要通过立体选择性分子内Diels-Alder反应构建六环碳骨架，然后进行自由基环化。随后，精心设计的氧化还原操作序列被优化，以实现这种高度氧化的Veratrum生物碱的从头合成。

据介绍，Veratrum生物碱是一种高度复杂的甾体生物碱，具有复杂的结构和立体化学特征，具有多种药理活性。

附：英文原文

Title: Enantioselective Total Synthesis of ()-Zygadenine

Author: Yinliang Guo, Jia-Tian Lu, Runting Fang, Yang Jiao, Jiaqi Liu, Tuoping Luo

Issue&Volume: September 8, 2023

Abstract: The Veratrum alkaloids are highly complex steroidal alkaloids characterized by their intricate structural and stereochemical features and exhibit a diverse range of pharmacological activities. A new synthetic pathway has been developed to access this family of natural products, which enabled the first total synthesis of ()-zygadenine. This synthetic route entails the construction of a hexacyclic carbon skeleton through a stereoselective intramolecular Diels–Alder reaction, followed by a radical cyclization. Subsequently, a meticulously designed sequence of redox manipulations was optimized to achieve the de novo synthesis of this highly oxidized Veratrum alkaloid.

DOI: 10.1021/jacs.3c08039

Source: https://pubs.acs.org/doi/10.1021/jacs.3c08039