Glutarimide

DescriptionGlutarimide, also known as Piperidine-2,6-dione or 2,6-Piperidinedione, is a versatile and commonly used organic reagent, classified in pharmacology as a protein synthesis inhibitor compound. It is also an important component of the anti-cancer drug thalidomide. The study reported the synthesis of triazoloquinoxaline derivative (Compound 15), a new potent anticancer drug containing a glutarimide molecule, based on the CRBN binding property of the glutarimide molecule in thalidomide molecule and the cytotoxic activity of triazole-quinoxaline. The IC50s were 9.81 ± 0.7, 15.49 ± 1.2 and 10.09 ± 0.9 μM for hepatocellular carcinoma (HepG2), prostate cancer (PC3) and breast cancer (MCF-7), respectively. It was superior to thalidomide in decreasing NF-κB P65 levels in HepG-2 cells[1].

UsesGlutarimide acts as an inhibitor of protein synthesis. Further, it is used as a reactant for thionations and biocatalytic asymmetric synthesis of sitagliptin production. It is also employed in the generation of beta-adrenoceptor ligands, enantioselective synthesis of securinega alkaloids and alfa-fluoro-alfa amino amides. In addition to this, it is used in intramolecular amidocyclopropanation reactions.

General DescriptionA glutarimide antibiotic, 9-methylstreptimidone, shows antiviral, antitumor and antifungal activities.

PreparationTo a flask containing 70 gm (0.53 mole) of glutaric acid is added 150 ml (2.2 mole) of 28% aqueous ammonia. The mixture is set for distillation and heated for 7 hr as the temperature of the mixture rises from 90° to 180°C. The temperature is held at 170-180°C for \\ hr or until the evolution of ammonia ceases. The reaction mixture solidifies on cooling and the pro­duct is recrystallized from acetone to afford 37.4 gm (63%), m.p. 145-146°C. t may be advantageous to preform the ammonium salt of dicarboxylic acids prior to the application of enough heat to form the imide. The preparation of succinimide is a case in point.