5 - Nitro-thiazol-2 - Carboxylic Acid And Biological Activity Of Derivatives

Aiming at the modification of the structure of the inhibitor for thymidylate synthase raltitrexed, we describe in the present dissertation the synthesis of 5-aminothiazole-2-carboxylic acid analogs which show good biological activity. The synthetic work started from 2-amino-5-nitrothiazole.2-Amino-5-nitrothiazole was successfully converted to N-[(5-nitro-2-thiazolyl)carbonyl]-L-glutamate via twice diazotizations followed by acylation and reduction reactions. The target compound was obtained in 17.5% overall yield for the five steps. The product was characterized by MS,1H NMR, 13C NMR, microelemental analysis along with the measurement of the specific rotation.In this thesis, we also developed a novel one-pot protocol for the synthesis of 5-nitrothiazole-2-carboxylic acid amide by employment of CuCN and t-BuONO. The amide was identified by means of MP, IR,1H NMR and MS. The improved process carries several advantages such as safe workup, high yield and mild condition, thus would be more promising for industrial application.We also developed a novel protocol for hydrogenation by using the catalyst of Pd(OH)2 on carbon while other palladium catalysts would lose their activity in case of sulfur-containing substrates. Upon screening, we found Pd(OH)2-C had a good ability of anti-poisoning on hydrogenation reaction (reduction of nitro and debenzylation).