SYNTHESIS OF AMINO-ACIDS WITH MODIFIED PRINCIPAL PROPERTIES .2. AMINO-ACIDS WITH POLAR SIDE-CHAINS

The synthesis and characterization of five new homochiral amino acids derived from L-serine are presented. In the modified amino acids, the side chain of serine has been elongated by the introduction of one or more ethyleneoxy moieties and the new compounds contain either a terminal hydroxy group or a terminal amino group. Full experimental details are given for the synthesis of the following amino acids: (2S)-2-amino-6-hydroxy-4-oxahexanoic acid, (2S)-2-amino-9-hydroxy-4,7-dioxanonanoic acid, (2S)-2-amino-12-hydroxy-4,7,10-trioxadodecanoic acid, (2S)-2,9-diamino-4,7-dioxanonanoic acid, and (2S)-2,12-diamino-4,7,10-trioxadodecanoic acid. These compounds were prepared with a view to obtaining amino acids which possess physical and chemical properties such that their principal properties would be different from previously known amino acids. The structural modifications were made with the objective of altering the principal properties related both to lipophilicity and to size. The principal properties are determined as latent variables in the principal component analysis of molecular property descriptors. Three new amino acids, (2S)-2-amino-9-hydroxy-4,7-dioxanonanoic acid, (2S)-2-amino-12-hydroxy-4,7,10-trioxadodecanoic acid and (2S)-2,12-diamino-4,7,10-trioxadodecanoic acid were found to have principal properties which are clearly different from those of previously known amino acids. The principal properties as measured by the principal component scores are given.