Synthesis of 2'-C-beta-fluoromethyluridine.
[reaction: see text] 2'-C-beta-Fluoromethyluridine (17) represents both a potentially important biological agent and a tool for biochemical analysis. Here we describe the first synthesis of this compound starting from uridine. The key steps include protection of the uracil base with methoxyethoxymethyl (MEM) chloride, conversion to the corresponding 2'-C-alpha-epoxide, and regioselective opening of the oxirane ring with potassium fluoride/hydrogen fluoride. Subsequent acetylation of the 3'- and 5'-hydroxyl groups enables MEM removal using B-bromocatecholborane. Deacetylation generates the parent nucleoside, 2'-C-beta-flurormethyluridine.
Dai
Qing
Q
Howard Hughes Medical Institute, Department of Biochemistry & Molecular Biology, The University of Chicago, 5841 S. Maryland Ave., MC 1028, Chicago, Illinois 60637, USA.
Piccirilli
Joseph A
JA
D004852:Epoxy Compounds / Q000138:chemical synthesis; D005459:Fluorides; D006858:Hydrofluoric Acid; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D017680:Potassium Compounds; D014498:Uracil / Q000737:chemistry; D014529:Uridine / Q000031:analogs & derivatives / Q000138:chemical synthesis*
C474369:2'-C-fluoromethyluridine; D004852:Epoxy Compounds; D007202:Indicators and Reagents; D017680:Potassium Compounds; D014498:Uracil; C033320:potassium fluoride; D005459:Fluorides; D006858:Hydrofluoric Acid; D014529:Uridine