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 févr. 2023
Accepted
24 mars 2023
First published
01 avr. 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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