Total Synthesis of Proteasome Inhibitor (−)-Omuralide through Asymmetric Ketene [2 + 2]-Cycloaddition

The total synthesis of (−)-omuralide, a potent specific proteasome inhibitor, has been achieved through an unprecedented route. The C3 and C4 chiral centers of the natural product have been selectively installed by an asymmetric [2 + 2]-cycloaddition between an unusual oxadisilinane ketene and a chiral enol ether, while the $\gamma$-lactam core was prepared by a single-pot two-step Beckmann transposition. The C5 quaternary center was eventually defined by an original selective oxidative desymmetrization of a spiro cyclic oxadisilinane thanks to the anchimeric assistance of a proximal hydroxyl group.

Références

Titre
Total Synthesis of Proteasome Inhibitor (−)-Omuralide through Asymmetric Ketene [2 + 2]-Cycloaddition
Type de publication
Article de revue
Année de publication
2018
Revue
Organic Letters
Volume
20
Pagination
4558–4561
Soumis le 29 août 2018