title: 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.
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.
authors.affiliation: Novartis Institutes for BioMedical Research, Lichtstrasse 35, WSJ-507.3.02, CH-4056 Basel, Switzerland. rainer.albert@novartis.com
authors.forename: Rainer
authors.initials: R
authors.lastname: Albert
authors.forename: Klaus
authors.initials: K
authors.lastname: Hinterding
authors.forename: Volker
authors.initials: V
authors.lastname: Brinkmann
authors.forename: Danilo
authors.initials: D
authors.lastname: Guerini
authors.forename: Constanze
authors.initials: C
authors.lastname: Müller-Hartwieg
authors.forename: Helmut
authors.initials: H
authors.lastname: Knecht
authors.forename: Corinne
authors.initials: C
authors.lastname: Simeon
authors.forename: Markus
authors.initials: M
authors.lastname: Streiff
authors.forename: Trixie
authors.initials: T
authors.lastname: Wagner
authors.forename: Karl
authors.initials: K
authors.lastname: Welzenbach
authors.forename: Frédéric
authors.initials: F
authors.lastname: Zécri
authors.forename: Markus
authors.initials: M
authors.lastname: Zollinger
authors.forename: Nigel
authors.initials: N
authors.lastname: Cooke
authors.forename: Eric
authors.initials: E
authors.lastname: Francotte
mesh_terms: D000276:Adjuvants, Immunologic / Q000097:blood*; D000818:Animals; D016466:CHO Cells; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D003412:Cricetulus; D018360:Crystallography, X-Ray; D000068876:Fingolimod Hydrochloride; D006801:Humans; D008297:Male; D010755:Organophosphates / Q000097:blood* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010766:Phosphorylation; D011409:Propylene Glycols / Q000097:blood*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D049349:Receptors, Lysosphingolipid / Q000819:agonists / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C453461:2-amino-2-(hydroxymethyl)-4-(4-octylphenyl)butyl phosphate; D000276:Adjuvants, Immunologic; D010755:Organophosphates; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine