SYNTHESIS OF A CHIRAL SERINE ALDEHYDE EQUIVALENT AND ITS CONVERSION TO CHIRAL ALPHA-AMINO-ACID DERIVATIVES

We report a new methodology for the synthesis of chiral nonproteinaceous alpha-amino acids, which involves protection of the carboxyl group of serine as a cyclic ortho ester. This reduces the acidity of the alpha-proton, allowing for oxidation of the side chain of serine to an aldehyde without racemization. A variety of carbonyl addition reactions, such as Grignard, Reformatsky, and Wittig additions, can then be carried out, leading to a wide range of amino acids. Very good stereocontrol is achieved, allowing for the selective synthesis of all four diastereomers of beta-hydroxy-alpha-amino acids. The method readily allows for stereospecific incorporation of both C and H isotopes in amino acid side chains.