Asymmetric synthesis of 5-substituted-1-(o-aryl)-2-thiobarbituric acid derivatives and their antibacterial activities

The main purpose of the study was to perform asymmetric synthesis of 5-substituted-1-(o-aryl)-2-thiobarbituric acid derivatives in order to obtain 5,5-dialkylsubstituted-1-(o-aryl)-2-thiobarbituric acid derivatives which are supposed to be biologically active. Many derivatives of barbituric acids act as central nervous system depressants, and can therefore produce a wide spectrum of effects, from mild sedation to total anesthesia. They are also effective as anxiolytics, hypnotics, analgesic and anticonvulsants. Among them, 2-thiobarbituric acid derivatives show a wide range of biological activity, so some of them are useful drugs or agrochemicals. Asymmetric synthesis is an essential process in the field of pharmaceuticals, as different enantiomers or diastereomers of the product often have different biological activity. In this study two types of alkylation reactions were performed as benzylation and allylation reactions. Asymmetric alkylation reactions were performed using (+)-cinchonine as chiral catalyst and enantio-and diastereoselectivity of the reactions in which stereoselective substitution took place at the fifth position of the heterocycle were determined using 1H and 13C NMR spectroscopies, normal phase HPLC and polarimeter. In addition, 5-methyl-1-phenyl-2-thiobarbituric acid was also alkylated to observe the effect of ortho-substituent of the aryl group on the enantioselectivity and diasteroselectivity of the reaction. Morever, antibacterial activities of all the synthesized 5,5-disubstituted-1-(o-aryl)-2-thiobarbituric acid derivatives and 5-substitued-1-(o-aryl)-2-thiobarbituric acid derivatives were measured against E. coli, B. subtiles, P. auregenause and S. aureus by disk diffusion method. Finally, the antibacterial effects of the product 5-benzyl-1(o-fluorophenyl)-2-thiobarbituric acid were identified against E. coli and P. aeruginosa by the same method.