Total Synthesis of (±)-Dhilirolide U

Journal of the American Chemical Society 2026

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Authors: Henrik R. Wilke, Marlene Fadel, Kacper J. Patej, Jan P Prohaska, Jonathan Kastner, V. S. Avramenko, Oscar García González, Rüveyda Bal, Matteo C Amberg, Jameel Ahmad, Nima Nasiri, Tobias K Jenny
+1 more Erick M Carreira
DOI: 10.1021/jacs.5c22734
Cited by: 3
References: 54

Abstract

We report the first total synthesis of (±)-dhilirolide U, a highly oxidized meroterpenoid featuring a densely functionalized 6/6/6/5/5-pentacyclic skeleton. Central to the strategy are a Mn III -mediated cyclization sequence and a Payne-type rearrangement cascade, which together forge a bicyclo[3.2.1]octane fused to a γ-lactone─the defining motif of the dhilirolide natural product family. Both transformations proceed in high yields and with excellent diastereocontrol. Intramolecular Ni-catalyzed conjugate addition was leveraged to install the vicinal quaternary carbon centers. This transformation set the stage for construction of the tetrahydroisochromenone subunit and completion of (±)-dhilirolide U. The reported route to the highly decorated bicyclo[3.2.1]octane provides a blueprint to access the diverse family that are the complex dhilirolide meroterpenoids.

Fields of Study & Subjects

Marine Sponges and Natural Products Natural Compound Pharmacology Studies Bioactive Natural Diterpenoids Research

Publication details

Journal / source
Journal of the American Chemical Society
Publisher
American Chemical Society (ACS)
Volume
148
Issue
6
Pages
5916–5922
Publication date
9 February 2026
Language
EN