Total Synthesis of Illisimonin A and Merrilactone A

• Published in: Angewandte Chemie International Edition 2023-08, Vol.62 (31), p.e202306367-n/a
• Main Authors: Gong, Xu, Huang, Juan, Sun, Xiangrui, Chen, Ziling, Yang, Ming
• Format: Article
• Language: English
• Subjects: Aldehydes; Axonogenesis; Biological activity; Desymmetrization; Illicium; Illicium Sesquiterpenes; Lactones; Metabolites; Molecular Structure; Natural Product Synthesis; Neurons; Oxidation; Phosphine; Phosphines; Plant species; Reductive Heck Reaction; Retro-Dieckmann Condensation; Secondary metabolites; Sesquiterpenes
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202306367

Illicium sesquiterpenes are a large family of biologically active secondary metabolites isolated from Illicium species of plants and are well‐known for their activity of neurite outgrowth in cultured neurons. Herein, we propose a comprehensive biosynthetic pathway for illicium sesquiterpenes and report a synthetic route to illisimonin A and merrilactone A based on it. We think that the carbon scaffolds of most of the illicium sesquiterpenes could be synthesized from a dicarbonyl derivative of allo‐cedrane through 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 with up to 82 % ee by an asymmetric intramolecular desymmetrizing reductive Heck reaction by the use of a new type of chiral phosphine ligand. The syntheses of illisimonin A and merrilactone A supported the key transformations of the proposed biosynthetic pathway. A comprehensive biosynthetic pathway was proposed for illicium sesquiterpenes. The key transformations of the biosynthetic pathway, which include retro‐Dieckmann condensation, oxidative cleavage and aldol reaction, were supported by the total syntheses of illisimonin A and merrilactone A from a common intermediate.