Chiral vinylphosphonate and phosphonate analogues of the immunosuppressive agent FTY720.
The first enantioselective synthesis of chiral isosteric phosphonate analogues of FTY720 is described. One of these analogues, FTY720-(E)-vinylphosphonate (S)-5, but not its R enantiomer, elicited a potent antiapoptotic effect in intestinal epithelial cells, suggesting that it exerts its action via the enantioselective activation of a receptor. (S)-5 failed to activate the sphingosine 1-phosphate type 1 (S1P(1)) receptor.
Lu
Xuequan
X
Department of Chemistry and Biochemistry, Queens College of The City University of New York, Flushing, New York 11367-1597, USA.
Sun
Chaode
C
Valentine
William J
WJ
Shuyu
E
E
Liu
Jianxiong
J
Tigyi
Gabor
G
Bittman
Robert
R
D000818:Animals; D002478:Cells, Cultured; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects; D015394:Molecular Structure; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry; D011409:Propylene Glycols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D049349:Receptors, Lysosphingolipid / Q000187:drug effects; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D014753:Vinyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
C542743:((E)-3-amino-5-(4-heptylphenyl)-3-(hydroxymethyl)pent-1-enyl)phosphonic acid; D007166:Immunosuppressive Agents; D063065:Organophosphonates; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D014753:Vinyl Compounds; C433467:vinylphosphonic acid; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine