Jump to Main Content
A facile tandem double-dehydrative-double-Heck olefination strategy for pot-economic synthesis of (E)-distyrylbenzenes as multi-target-directed ligands against Alzheimer's disease employing C. elegans model
- Andhare, Nitin H., Thopate, Yogesh, Shamsuzzama,, Kumar, Lalit, Sharma, Tanuj, Siddiqi, M.I., Sinha, Arun K., Nazir, Aamir
- Tetrahedron 2018 v.74 pp. 1655-1667
- Alzheimer disease, Caenorhabditis elegans, acetylcholinesterase, amyloid, benzene, bromine, catalysts, chemical structure, enzyme inhibition, genetically modified organisms, hydroxylation, ionic liquids, ligands, lipids, molecular models, palladium, polymerization, reactive oxygen species, receptors, regioselectivity
- A concise, one pot and regioselective access to (E)-distyrylbenzenes (DSBs) from arylhalide and secondary phenylenediethanol, a stable precursor for in situ generation of divinylbenzene (DVB) to avoid its polymerization, is described for construction of double CC bond formation via tandem double-dehydrative-double-Heck (D-D-D-H) reaction using Palladium and ionic liquid [hmim]Br as a cooperative catalyst. It is noteworthy that this pot-economy approach also provides direct synthesis of hydroxylated distyrylbenzenes without requirement of protection-deprotection strategy. Importantly, the synthesized DSBs are tested for their protective activity against β amyloid reduction, acetylcholine esterase inhibition, lipid lowering and reactive oxygen species (ROS) reduction properties in transgenic Caenorhabditis elegans model wherein 1,3-bis((E)-4-(trifluoromethyl)styryl)benzene (5c) is found to be active across all above factors thus presenting lead molecule within multi-target-directed ligands (MTDLs) approach. Molecular docking studies were also performed to understand the interactions of potent DSBs with receptors.