The Synthesis and Crystal Structures of the Homologues of Epalrestat

Abstract

Two homologues of epalrestat were synthesized and characterized by IR, MS, elemental analysis, 1H NMR, 13C NMR and their crystal structures were determined by X-ray diffraction method. The crystals of both compounds belong to the triclinic centrosymmetric space group. In both crystal structures the carboxyl groups are involved in the strong O–H···O hydrogen bonds. One compound crystallizes together with the dimethylformamide molecules from the solvent, forming with them intermolecular hydrogen bonds. In this crystal structure the disorder of solvent molecule is observed. The packing of the second compound is determined by hydrogen bonds between carboxyl groups leading to formation of characteristic molecular pairs. In addition, the crystal structures are also stabilized by weak contacts C–H···O and C–H···S. Both crystal structures were compared to that of the epalrestat determined earlier. The investigated compounds differ in planarity of molecules in comparison to epalrestat, but the same isomer and the extended conformation as in epalrestat molecule, are observed. To study the conformations and intermolecular interactions of potential inhibitors of aldose reductase two homologues of epalrestat were synthesized and their crystal structures were determined by single crystal X-ray diffraction method. The first homologue forms strong hydrogen bonds via carboxyl group with DMF from the solvent, whereas the second builds homosynthons by intermolecular interaction of two molecules via carboxyl groups.