Synthesis & evaluation of substrate analogs for human & bacterial kynureninase and synthesis and stability studies of caged kynurenine

The present dissertation includes five chapters: Chapter 1 includes the introduction to tryptophan and the enzyme kynureninase, along with literature reviewChapter 2 includes the synthesis of the various substrate analogs of the enzyme kynureninase. A detailed synthetic method for the preparation of the racemic 3-chloro, 3-fluoro, 3-methyl, 5-bromo, and 5-chloro kynurenines has been described in this chapter. The racemic 3-chloro, 3-fluoro, and 3-methyl kynurenines have been prepared starting from the corresponding o-substituted anilines. A diazotization of these anilines followed by a stannous chloride reduction gives the corresponding 2-substituted phenylhydrazines. Reaction of the phenylhydrazines with the Michael adduct of diethyl acetamidomalonate and acrolein give the corresponding 2-substituted phenylhydrazone derivatives. These phenylhydrazone derivatives are then subjected to a Fischer indole cyclization to give the 3,7-disubstituted indoles. Ozonolysis of the indoles followed by acid hydrolysis affords the racemic kynurenines. The 5-bromo-L-kynurenine and 5-chloro-L-kynurenine have been prepared from L-tryptophan.Chapter 3 includes the results and discussion of the steady state kinetic studies of the synthesized substrate analogsChapter 4 includes the synthesis of a caged kynurenines and its stability studies using HPLCChapter 5 includes Conclusions