Synthesis and immobilization of erythro-C14-omega-aminosphingosine-1-phosphate as a potential tool for affinity chromatography.
A sphingosine-1-phosphate (S1P) analogue containing a terminal alkyl chain amino group is synthesized in a few steps via olefin cross-metathesis of an optically resolved intermediate and subsequent phosphorylation. Regioselective acylation of this intermediate at its N terminus in solution is demonstrated as a model reaction and provides a biologically active derivative. Finally, the omega-amino intermediate is immobilized on an affinity matrix. The choice of a UV-active phosphate protecting group allows for quantification of resin loading after cleavage which amounted to 66 %.
Ullrich
Thomas
T
Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Brunner Strasse 59, 1230 Wien, Austria. thomas.ullrich@novartis.com
Ghobrial
Michael
M
Peters
Carsten
C
Billich
Andreas
A
Guerini
Danilo
D
Nussbaumer
Peter
P
D000215:Acylation; D000475:Alkenes / Q000737:chemistry*; D001665:Binding Sites; D002846:Chromatography, Affinity / Q000379:methods*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004912:Erythrocytes / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008246:Lysophospholipids; D008956:Models, Chemical; D010766:Phosphorylation; D013110:Sphingosine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D013237:Stereoisomerism; D014471:Umbilical Veins / Q000166:cytology
D000475:Alkenes; D003432:Cross-Linking Reagents; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine