title: Synthesis, stereochemical determination and biochemical characterization of the enantiomeric phosphate esters of the novel immunosuppressive agent FTY720.
abstract: The novel immunosuppressive agent FTY720 (1) is phosphorylated in vivo in a variety of species yielding an active metabolite that is an agonist of four of the five known G-protein-coupled sphingosine-1-phosphate (S1P) receptors. A synthesis amenable to producing gram quantities of the stereoisomeric phosphate esters, a determination of their absolute stereochemistry via an enantioselective synthesis and their characterization as S1P receptor agonists and antagonists is reported.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. jeffrey_hale@merck.com
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Hale
authors.forename: Lin
authors.initials: L
authors.lastname: Yan
authors.forename: William E
authors.initials: WE
authors.lastname: Neway
authors.forename: Richard
authors.initials: R
authors.lastname: Hajdu
authors.forename: James D
authors.initials: JD
authors.lastname: Bergstrom
authors.forename: James A
authors.initials: JA
authors.lastname: Milligan
authors.forename: Gan-Ju
authors.initials: GJ
authors.lastname: Shei
authors.forename: Gary L
authors.initials: GL
authors.lastname: Chrebet
authors.forename: Rosemary A
authors.initials: RA
authors.lastname: Thornton
authors.forename: Deborah
authors.initials: D
authors.lastname: Card
authors.forename: Mark
authors.initials: M
authors.lastname: Rosenbach
authors.lastname: HughRosen
authors.forename: Suzanne
authors.initials: S
authors.lastname: Mandala
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000138:chemical synthesis*; D008968:Molecular Conformation; D010755:Organophosphates / Q000138:chemical synthesis*; D011409:Propylene Glycols / Q000138:chemical synthesis*; D013110:Sphingosine / Q000031:analogs & derivatives
chemical_list: D007166:Immunosuppressive Agents; D010755:Organophosphates; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine