SYNTHESIS OF AMINO-ACIDS WITH MODIFIED PRINCIPAL PROPERTIES .1. AMINO-ACIDS WITH FLUORINATED SIDE-CHAINS

The synthesis and characterization of chiral fluorinated analogues of norvaline and norleucine from commercially available starting materials are presented. Full experimental details for the synthesis of the following amino acids are given: (S)-4,4-difluoronorvaline, (S)-4,4,5,5,5-pentafluoronorvaline, (S)-5,5-difluoro-norleucine, (S)-5,5,6,6,6-pentafluoronorleucine, and (S)-4,4,5,5,6,6,6-heptafluoro-norleucine. These compounds were prepared with a view to obtaining new amino acids which possess physical and chemical properties so that their principal properties would be outside the range of variation of hitherto known amino acids. The principal properties are determined as latent variables in principal component analysis of molecular property descriptors. Two of the fluorinated amino acids, (S)-5,5,6,6,6-pentafluoronorleucine and (S)-4,4,5,5,6,6,6-heptafluoronorleucine were found to have principal properties outside the variation of previously characterized natural and synthetic amino acids. The principal properties, z parameters, for the five new fluorinated amino acids are given.