Enantioselective Total Syntheses of Manginoids A and C and Guignardones A and C

• Published in: Angewandte Chemie 2021-07, Vol.133 (28), p.15414-15418
• Main Authors: Zong, Yan, Xu, Ze‐Jun, Zhu, Rong‐Xiu, Su, Ai‐Hong, Liu, Xu‐Yuan, Zhu, Ming‐Zhu, Han, Jing‐Jing, Zhang, Jiao‐Zhen, Xu, Yu‐Liang, Lou, Hong‐Xiang
• Format: Article
• Language: English
• Subjects: asymmetric synthesis; Chemistry; cyclization; Divergence; Enantiomers; meroterpenoid; natural products; Silica; Silica gel; Silicon dioxide; total synthesis
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202104182

An enantioselective synthetic approach for preparing manginoids and guignardones, two types of biogenetically related meroterpenoids, is reported. This bioinspired and divergent synthesis employs an oxidative 1,3‐dicarbonyl radical‐initiated cyclization and cyclodehydration of the common precursor to forge the central ring of the manginoids and guignardones, respectively, at a late stage. Key synthetic steps include silica‐gel‐promoted semipinacol rearrangement to form the 6‐oxabicyclo[3.2.1]octane skeleton and the Suzuki–Miyaura reaction of vinyl bromide to achieve fragment coupling. This synthesis protocol enables the asymmetric syntheses of four fungal meroterpenoids from commercially available materials. The enantioselective total syntheses of fungal meroterpenoids, manginoids A and C, as well as guignardones A and C, are accomplished. This divergent and bioinspired synthetic strategy involves a Csp3−Csp2 Suzuki–Miyaura coupling of vinyl bromide, silica‐gel‐promoted semipinacol rearrangement, and oxidative 1,3‐dicarbonyl radical‐initiated cyclization.