Bioinspired Network Analysis Enabled Divergent Syntheses and Structure Revision of Pentacyclic Cytochalasans. Issue 29 (17th June 2021)

• Record Type: Journal Article
• Authors: Wu, Hai; Ding, Yiming; Hu, Kun; Long, Xianwen; Qu, Chunlei; Puno, Pema‐Tenzin; Deng, Jun
• Is Part Of: Angewandte Chemie international edition. Volume 60:Issue 29(2021)
• Page Start: 15963
• Page End: 15971
• Publication Date: 2021-06-17
• Subjects: bioinspired network analysis -- biomimetic synthesis -- natural products -- pentacyclic cytochalasans -- structure elucidation; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202102831
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: We accomplished the divergent total syntheses of ten pentacyclic cytochalasans (aspergillin PZ, trichodermone, trichoderones, flavipesines, and flavichalasines) from a common precursor aspochalasin D and revised the structures of trichoderone B, spicochalasin A, flavichalasine C, aspergilluchalasin based on structure network analysis of the cytochalasans biosynthetic pathways and DFT calculations. The key steps of the syntheses include transannular alkene/epoxyalkene and carbonyl‐ene cyclizations to establish the C/D ring of pentacyclic aspochalasans. Our bioinspired approach to these pentacyclic cytochalasans validate the proposed biosynthetic speculation from a chemical view and provide a platform for the synthesis of more than 400 valuable cytochalasans bearing different macrocycles and amino‐acid residues. Abstract : The bioinspired, divergent total syntheses of trichodermone and trichoderone A were accomplished from a common biogenetic precursor, aspochalasin Z. Key steps include transannular alkene cyclizations, a singlet oxygen ene reaction, and hydrogen atom transfer (HAT) cascade reactions. This approach validates the proposed biosynthetic pathway from a chemical perspective and paves the way for the synthesis and characterization of other cytochalasans.