AI Article Synopsis
- - Oxindoles and iso-oxindoles are natural compounds that could lead to the creation of new biologically important classes of compounds, especially through combining them into spirocyclic structures, which nature hasn't fully utilized yet.
- - The study presents a selective method using Rh-catalysis to create diverse spirooxindole-isooxindole and spirooxindole-oxindole compounds from specially protected diazooxindoles and N-pivaloyloxy aryl amides, showcasing a key rearrangement process.
- - Through the Cell Painting assay, researchers identified the mitotic kinesin Eg5 as a primary target for spirooxindoles, establishing them as a new type of inhibitor
Article Abstract
Oxindoles and iso-oxindoles are natural product-derived scaffolds that provide inspiration for the design and synthesis of novel biologically relevant compound classes. Notably, the spirocyclic connection of oxindoles with iso-oxindoles has not been explored by nature but promises to provide structurally related compounds endowed with novel bioactivity. Therefore, methods for their efficient synthesis and the conclusive discovery of their cellular targets are highly desirable. We describe a selective Rh -catalyzed scaffold-divergent synthesis of spirooxindole-isooxindoles and spirooxindole-oxindoles from differently protected diazooxindoles and N-pivaloyloxy aryl amides which includes a functional group-controlled Lossen rearrangement as key step. Unbiased morphological profiling of a corresponding compound collection in the Cell Painting assay efficiently identified the mitotic kinesin Eg5 as the cellular target of the spirooxindoles, defining a unique Eg5 inhibitor chemotype.
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| http://dx.doi.org/10.1002/anie.202301955 | DOI Listing |
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