Total Synthesis of Anti‐Cancer Meroterpenoids Dysideanone B and Dysiherbol A and Structural Reassignment of Dysiherbol A

• Published in: Angewandte Chemie Vol. 133; no. 25; pp. 13926 - 13932
• Main Authors: Chong, Chuanke, Zhang, Qunlong, Ke, Jia, Zhang, Haiming, Yang, Xudong, Wang, Bingjian, Ding, Wei, Lu, Zhaoyong
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 14.06.2021
• Subjects: Alkylation; Benzyl bromide; Cancer; Chemical reactions; Chemical synthesis; Chemistry; Divergence; dysideanone B; dysiherbol A; Ethanol; meroterpenoids; natural products; Stereoselectivity; structure elucidation
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202100541

The first total synthesis of marine anti‐cancer meroterpenoids dysideanone B and dysiherbol A have been accomplished in a divergent way. The synthetic route features: 1) a site and stereoselective α‐position alkylation of a Wieland–Miescher ketone derivative with a bulky benzyl bromide to join the terpene and aromatic moieties together and set the stage for subsequent cyclization reactions; 2) an intramolecular radical cyclization to construct the 6/6/6/6‐tetracycle of dysideanone B and an intramolecular Heck reaction to forge the 6/6/5/6‐fused core structure of dysiherbol A. A late‐stage introduction of the ethoxy group in dysideanone B reveals that this group might come from the solvent ethanol. The structure of dysiherbol A has been revised based on our chemical total synthesis. The first total synthesis of marine anti‐cancer natural products dysideanone B and dysiherbol A have been completed and the structure of dysiherbol A has been revised. A radical cyclization was employed to construct the 6/6/6/6 skeleton of dysideanone B and a Heck reaction was utilized to forge the 6/6/5/6 core structure of dysiherbol A.