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Published on: September 21, 2019
Total Synthesis of Proteasome Inhibitor (-)-Omuralide through Asymmetric Ketene [2 + 2]-Cycloaddition
Pauline Rullière1,2, Alexandre Cannillo1,2, Julien Grisel1,2
1Univ. Grenoble Alpes, DCM , F-38000 Grenoble , France.
Abstract:
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 γ-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.
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