Author: Cheng Minjing 

Publisher: College of Pharmacy  

Date: March 11, 2025

Jinan University Integrated Media Center News: Highly functionalized anthraquinone compounds exhibit significant biological activity, but their synthesis poses challenges due to complex ring structures, multiple chiral centers, and high oxidation states. The research team led by Ye Wencai, Wang Lei, and Cheng Minjing at Jinan University developed a chiral separation method through photo-extension reactions, achieving the first asymmetric total synthesis of various oxanthracene natural products (Nat. Commun. 2024, 15, 5879).

(Screenshot of the paper)

Recently, to eliminate reliance on chiral separation methods, the team proposed a photocatalytic skeleton rearrangement strategy inspired by the structure of the spiro natural product myrtuspirone A (Org. Lett. 2019, 21, 1583). This novel approach successfully enabled the first asymmetric total synthesis of myrtucomvalones E-F. Collaborating with Associate Researcher Liu Chang, the team discovered a compound with significant anti-osteosarcoma activity, with the findings published in Angewandte Chemie International Edition (DOI: 10.1002/anie.202420671). Co-first authors of the paper include Lin Shilin (doctoral student), Zhao Fen (master's student), and Wei Fen (also from Jinan University).

 Key Findings:

The research highlights a unique ketyl radical-induced skeletal rearrangement reaction of spirodihydrobenzofurans, facilitated by zero-valent iron agents through photoredox catalysis. This method allows for the simplified preparation of various highly functionalized xanthenes, showcasing notable features such as:

- High chemo- and regioselectivity

- Mild reaction conditions

- Broad substrate scope

- Scalability to gram-scale quantities

- Consistently good to excellent yields

 Mechanistic Insights:

The authors conducted extensive screening to determine optimal conditions for the photocatalytic skeleton rearrangement reaction, testing spirocyclic substrates with different substituents. The results confirmed that this method efficiently synthesizes diverse oxanthracene compounds rapidly. Using this approach, the asymmetric synthesis of myrtucomvalones E-F—a complex anthracene-derived natural product—was achieved in just 6-7 steps.

In exploring the reaction mechanism, stereochemical properties were verified through hydrogen transfer experiments, indicating no racemization occurred. Additional experiments, including light on/off tests and free radical capture, elucidated the potential mechanisms behind the photocatalytic rearrangement.

This paper introduces a groundbreaking strategy for photocatalytic skeleton rearrangement, successfully synthesizing a series of highly functionalized oxanthracene compounds, and discovering agents with significant anti-osteosarcoma activity. These findings offer a scientific basis for developing new anti-osteosarcoma drugs.

Read the full paper: [Angew Chem Int Ed]

( https://doi.org/10.1002/anie.202420671)