Novel immunomodulator FTY720 is phosphorylated in rats and humans to form a single stereoisomer. Identification, chemical proof, and biological characterization of the biologically active species and its enantiomer

  • J Med Chem. 2005 Aug 11;48(16):5373-7. doi: 10.1021/jm050242f.
Rainer Albert  1 ,  Klaus Hinterding ,  Volker Brinkmann ,  Danilo Guerini ,  Constanze Müller-Hartwieg ,  Helmut Knecht ,  Corinne Simeon ,  Markus Streiff ,  Trixie Wagner ,  Karl Welzenbach ,  Frédéric Zécri ,  Markus Zollinger ,  Nigel Cooke ,  Eric Francotte
Affiliations
  • 1. Novartis Institutes for BioMedical Research, Lichtstrasse 35, WSJ-507.3.02, CH-4056 Basel, Switzerland. [email protected]
PMID: 16078855 DOI: 10.1021/jm050242f
Abstract

In vivo phosphorylation of FTY720 (1) in rats and humans resulted exclusively in the biologically active (S)-configured enantiomer, which was proven by an ex vivo o-phthaldialdehyde derivatization protocol especially elaborated for phosphates of 1. Starting from the prochiral amino alcohol 1, racemic and enantiomerically pure phosphates of 1 were synthesized. Pure enantiomers were obtained after purification of a partially protected key intermediate on an enantioselective support. The absolute stereochemistry was determined by X-ray diffraction.