Diastereoselective Three-Component Cascade Reaction to Construct Oxindole-Fused Spirotetrahydrofurochroman Scaffolds for Drug Discovery

A one-pot synthesis of new oxindole-fused polycyclic scaffolds is reported. The process involves a three-component [3+2] cycloaddition followed by cyclization through an intramolecular Michael addition. The reaction gives easy access to oxindole-fused spirotetrahydrofurochromans in moderate to good yields with high regio- and diastereoselectivity. These compounds could be useful for for drug discovery. Further modification was achieved by reduction of the nitro group, and intramolecular amide formation to give the corresponding lactams. The resulting heterocyclic products show good inhibitory activity against the enzyme PTP1B in vitro. A one-pot three-component cascade reaction involving a [3+2] cycloaddition followed by a cyclization through intramolecular Michael addition was used to generate two families of oxindole-fused spirotetrahydrofurochroman polyheterocycles with high regio- and diastereoselectivity. The resulting polycyclic products were found to inhibit the enzyme PTP1B in vitro.