兰州大学阳铭团队报道了IllisimoninA和 Merrilactone A的全合成。相关研究成果于2023年6月5日发表在国际顶尖学术期刊《德国应用化学》。

八角倍半萜是从八角属植物中分离出来的大量具有生物活性的次生代谢产物，以其在培养神经元中突起生长的活性而闻名。和对八角倍半萜的生物活性和合成的各种研究相比，对其生物合成途径的研究很少。

该文中，研究人员报道了一条合理的八角倍半萜的综合生物合成途径，并在此基础上合成了illisimonin A和merrillactone A，自然中合适氧化态下的氧化裂解和羟醛反应。通过分子内去对称还原Heck反应组装了类似于allo cedrane的二羰基衍生物的illisimonin A和Merrillactone A的常见中间体。开发了一种新型的手性膦配体来实现不对称分子内去对称还原Heck反应，获得了最高82%的ee。Illisimonin A和Merrillactone A的合成证实了所提出的生物合成途径的关键转化。

附：英文原文

Title: Total Synthesis of Illisimonin A and Merrilactone A

Author: Xu Gong, Juan Huang, Xiangrui Sun, Ziling Chen, Ming Yang

Issue&Volume: 2023-06-05

Abstract: Illicium sesquiterpenes are a large number of biologically active secondary metabolites which are isolated from Illicium species of plants and well known for their activity of neurite outgrowth in cultured neurons. Compared to various studies of bioactivity and synthesis of the illicium sesquiterpenes, there are very few discussions in their biosynthetic pathways. Herein, we report a plausible comprehensive biosynthetic pathway of illicium sesquiterpenes and a synthetic route to illisimonin A and merrilactone A based on it. We think that most of the illicium sesquiterpenes’ carbon scaffolds could be synthesized from dicarbonyl derivative of allo-cedrane via retro-Dieckmann condensation, oxidative cleavage and aldol reaction at suitable oxidation states in Nature. The common intermediate for illisimonin A and merrilactone A similar to the dicarbonyl derivative of allo-cedrane was assembled by an intramolecular desymmetrizing reductive Heck reaction. A new type of chiral phosphine ligands was developed to achieve the asymmetric intramolecular desymmetrizing reductive Heck reaction, and a maximum of 82% ee was obtained. The syntheses of illisimonin A and merrilactone A confirmed the key transformations of the proposed biosynthetic pathway.

DOI: 10.1002/anie.202306367

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202306367