澳大利亚国立大学Michael Sherburn团队报道了千屈菜次碱的五步全合成策略。相关研究成果于2021年6月22日发表在《德国应用化学》。

本文报道了千屈菜次生物碱的简明合成方法。该策略通过双向合成方法利用目标的局部C2对称性，首先在非循环环境中，然后在循环系统中，最后在桥接大环域中。后一阶段合成的安装所有四个立体中心的相，涉及热力学控制，两倍分子间/跨环氮杂Michael加成和两倍氢化物还原。

该合成是以前最经济一步方法长度的三分之一，提供了获得克量天然产物的途径。通过制备天然产物的三种非对映异构体类似物，证明了合成的广谱性质。

附：英文原文

Title: Five Step Total Synthesis of Lythranidine

Author: Michael Sherburn, Nicholas L. Magann, Mitchell T. Blyth

Issue&Volume: 2021-06-22

Abstract: A concise synthesis of the alkaloid lythranidine is reported. The strategy exploits the target’s local  C  2  symmetry by adopting a two directional synthetic approach, first in an acyclic environment, then in a cyclic system and finally in a bridged macrocyclic domain. The latter phase of the synthesis, which installs all four stereocenters, involves a thermodynamically controlled, twofold intermolecular/transannular aza-Michael addition and a twofold hydride reduction. The synthesis is one third of the length of the most step-economic previous approach, providing access to gram quantities of the natural product. The broad-spectrum nature of the synthesis is demonstrated through the preparation of three diastereomeric analogues of the natural product.

DOI: 10.1002/anie.202107524

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202107524