(1-benzylpiperazin-2-yl)methanols:: novel EPC synthesis from (S)-serine and transformation into ligands for central nervous system receptors

A novel three-step synthesis of 4-substituted-(1-benzyipiperazin-2-yl)methanols 5a-5c is described starting from the methyl ester of the proteinogenic amino acid (S)-serine, which involves the diastereomeric oxazolidine derivatives 11a-11c as key intermediates. 5b and 5e were transformed into the chiral, non-racemic bicyclic lactams 14b and 14e via Swern oxidation followed by Wittig reaction and subsequent hydrogenation. In the screening for central nervous system receptor affinity the butyl derivative 14b was found to have promising interaction with sigma (1)-receptors (K-i = 345 nM). (C) 2001 Elsevier Science Ltd. All rights reserved.