Issue 18, 2023

Total synthesis of (−)-scabrolide A and (−)-yonarolide

Abstract

The complete account of the total syntheses of scabrolide A and yonarolide is disclosed. This article describes an initial approach involving a bio-inspired macrocyclization/transannular Diels–Alder cascade, which ultimately failed due to undesired reactivity during macrocycle construction. Next, the evolution of a second and third strategy, which both involve an initial intramolecular Diels–Alder reaction followed by a late-stage closure of the seven-membered ring of scabrolide A are detailed. The third strategy was first validated on a simplified system, but problems were encountered during a key [2 + 2] photocycloaddition on the fully elaborated system. An olefin protection strategy was employed to circumvent this problem, ultimately leading to the completion of the first total synthesis of scabrolide A and the closely related natural product yonarolide.

Graphical abstract: Total synthesis of (−)-scabrolide A and (−)-yonarolide

Supplementary files

Article information

Article type
Edge Article
Submitted
05 2 2023
Accepted
24 3 2023
First published
01 4 2023
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2023,14, 4745-4758

Total synthesis of (−)-scabrolide A and (−)-yonarolide

N. J. Hafeman, S. A. Loskot, C. E. Reimann, B. P. Pritchett, S. C. Virgil and B. M. Stoltz, Chem. Sci., 2023, 14, 4745 DOI: 10.1039/D3SC00651D

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