Rhodanine-Furan Bis-Heterocyclic Frameworks Synthesis via Green One-Pot Sequential Six-Component Reactions: A Synthetic and Computational Study

摘要

Combinatorial construction of a drug-like library of novel rhodanine-furan bis-heterocyclic scaffolds has been demon- strated through a novel one-pot sequential six-component reaction in water under ultrasound irradiation with 100% atom economy. The process is a sequence of tandem Michael reactions followed by domino cycloaddition/zwitterionic ad- duct formation/Mumm rearrangement/[1+4] cycloaddition processes, involving diverse primary amines, carbon disulfide, maleic anhydride, dialkyl acetylenedicarboxylates and various isocyanides. No catalyst was required, but the use of aqueous two-phase (on water) conditions was critical. Docking and molecular dynamics calculations performed on human aldose reductase suggest that the bis-heterocyclic frameworks formed may be useful inhibitors of this enzyme.