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

Abstract

Combinatorial construction of a drug‐like library of novel rhodanine‐furan bis‐heterocyclic scaffolds has been demonstrated 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 adduct 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.

Novel Scaffolds Based on Bis-thiazole Connected to Quinoxaline or Thienothiophene through 2-Phenoxy-N-arylacetamide Groups as New Hybrid Molecules: Synthesis, Antibacterial Activity, and Molecular Docking Investigations

“…In addition to the prospective applications of thieno­[2,3- b ]­thiophene derivatives in optical and electrical systems, they have also sparked significant medicinal interest due to their diverse biological properties, which include antibacterial, antiviral, anticancer, and antiglaucoma properties. − Furthermore, bis-heterocyclic compounds are widely used as scaffolds in drugs and pharmaceutically relevant substances. Many bis-heterocycles have been shown to have anticancer, antibacterial, antiallergic, and other disease-fighting characteristics when linked properly. , Molecular hybridization is the process of combining at least two pharmacophore fragments from different bioactive chemicals to create hybrids that outperform the original drugs. The pharmacophore scaffolds of several compounds are combined to create hybrid molecules.…”

Sustainable synthesis of structures containing quinoxaline-pseudopeptide-triazole pharmacophoresviaa one-pot six-component reaction

“…Because of our interests in the design of combinatorial MCRs 28 and inspired by the above-discussed biological importance of structures containing quinoxaline-pseudopeptide-triazole functionalities, herein, we report a sustainable one-pot, six-component, tandem cyclocondensation/Ugi/click reaction sequence based on the higher-order MCR strategy to economically unify all three pharmacophoric elements into a sole structure.…”

Fusion of Cellulose and Multicomponent Reactions: Benign by Design

“…43 Besides that, more importantly, green metrics are taken into account in evaluating the greenness of the synthetic strategies. In this line, some of the attractive features of MCRs are that not only are they considered as a pot, atom, and step economy (PASE) strategy 44 but they also enjoy appropriate atom economy 45 introduced by Barry Trost 46 and environmental factor or E-factor (kg (waste)/kg (product)) developed by Roger Sheldon. 47 As a matter of fact, atom economy means how much of the atoms of the starting materials end up in the desired product.…”