No abstract

The merging of two or more known natural product-based scaffolds is a powerful and routine strategy to develop bioactive small molecules.

An efficient strategy for stereo-controlled synthesis of potential biological and structurally complex chromanone-based spirocyclohexaneoxindoles via an organocatalytic domino formal double Michael cycloaddition of bifunctional chromone-oxindole synthons and nitroolefins is reported. These products possessing five adjacent stereocenters including one spiro quaternary carbon center, were smoothly afforded in up to 85% yield, >99% ee, and >20:1 dr. This strategy benefits from the intramolecular nature of the second Michael reaction step, through counterbalancing the lower electrophilicity of these unactivated chromones to facilitate the reaction.

A highly efficient strategy for stereocontrolled construction of potentially bioactive and structurally rigid isoxazole‐fused spirocyclohexane oxindole‐based hexahydroxanthones via an organocatalytic domino Michael/Michael cycloaddition of multifunctional chromone‐based oxindole as a 4C building block and 3‐methyl‐4‐nitro‐5‐alkenyl‐isoxazole as an activated Michael acceptor is reported. Complex and skeleton‐diversified hexahydroxanthones bearing five continuous stereocenters including one spiro quaternary carton center were smoothly afforded in up to 92% yield, >20:1 d.r. and >99% ee. Further transformation of the product into other potentially bioactive molecules has also been demonstrated. This method could also forge the libraries of medicinally relevant molecules with skeletal diversity, thus to facilitate the search for new bioactive entities.magnified image