SYNTHESIS OF AMINO-ACIDS WITH MODIFIED PRINCIPAL PROPERTIES .3. SULFUR-CONTAINING AMINO-ACIDS

The synthesis and characterization of seven medium-sized, medium-polar , sulfur-containing amino acids are presented. The compounds were prep ared with the objective of finding amino acids which possess physical and chemical properties such that their principal properties would be clearly different from those of previously known amino acids. The prin cipal properties are determined as latent variables in principal compo nent analysis of molecular property descriptors.The following amino ac ids were prepared in homochiral form from L-cysteine: (2R)-2-amino-3-( 2-hydroxyethylsulfanyl)propanoic acid, (2R)-2-amino-3-(2-hydroxyethyls ulfonyl)propanoic acid, (3R)-perhydro-1,4-thiazine-3-carboxylic acid a nd (3R)-1,1-dioxoperhydro-1,4-thiazine-3-carboxylic acid. (3R)-1-Oxope rhydro-1,4-thiazine-3-carboxylic acid was prepared in NC protected for m, but all attempts to obtain the free amino acid failed. The principa l properties of this amino acid were determined on the racemic diaster eomers obtained by oxidation of the racemic perhydro-1,4-thiazine-3-ca rboxylic acid prepared from 2-aminoethanethiol and ethyl 3-bromo-2-oxo propanoate. With the exception of (3R)-perhydro-1,4-thiazine-3-carboxy lic acid for which the synthesis has been previously described, the am ino acids described are new compounds. An improved synthesis of (3R)-p erhydro-1,4-thiazine-3-carboxylic acid via the cyclization of (2R)-ben zyl 2-amino-3-(2-hydroxyethylsulfanyl)propanoate under Mitsunobu condi tions is presented. Full experimental details for the syntheses are gi ven. The principal property scores of the synthesized sulfur-containin g amino acids and of the structurally related 3-(2-aminoethyl)cysteine which was commercially available are given.