Synthesis of the Four Stereoisomers of 1‐Amino‐2‐(hydroxymethyl)cyclobutanecarboxylic Acid and Their Biological Evaluation as Ligands for the Glycine Binding Site of the NMDA Receptor

Abstract

Abstract A synthesis of all four stereoisomers [(1 S ,2 S )‐, (1 R ,2 R )‐, (1 S ,2 R )‐, (1 R ,2 S )‐] of 1‐amino‐2‐(hydroxymethyl)cyclobutanecarboxyclic acid is presented. The synthesis is based on the chiral glycine equivalent 1 , employed in both enantiomeric forms. The key step involves the cyclization of the silyl‐protected iodohydrins 5a − d to the corresponding spiro derivatives 6a − d with the aid of the phosphazenic base t Bu‐P 4 . The final compounds were found to display moderate potency as ligands for the glycine binding site of the NMDA receptor. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)