Addition of difluorocarbene to 3',4'-unsaturated nucleosides: synthesis of 2'-deoxy analogues with a 2-oxabicyclo[3.1.0]hexane framework.
Treatment of protected 2'-deoxy-3',4'-unsaturated nucleosides derived from adenosine and uridine with difluorocarbene [generated from bis(trifluoromethyl)mercury and sodium iodide] gave fused-ring 2,2-difluorocyclopropane compounds. Stereoselective alpha-face addition to the dihydrofuran ring resulted from hindrance by the protected beta-anomeric nucleobases. A protected uracil compound was converted smoothly into the cytosine derivative via a 4-(1,2,4-triazol-1-yl) intermediate. Removal of the protecting groups gave new difluorocyclopropane-fused nucleoside analogues. The solid-state conformation of the nearly planar furanosyl ring in the uracil compound had a shallow 2E pucker, and a more pronounced 1E conformation was present in the furanosyl ring of the cytosine derivative.
Nowak
Ireneusz
I
Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah 84602-5700, USA.
Cannon
John F
JF
Robins
Morris J
MJ
D001643:Bridged Bicyclo Compounds / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003510:Cyclohexanes / Q000737:chemistry*; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry*
C518114:2-oxabicyclo(3.1.0)hexane; D001643:Bridged Bicyclo Compounds; D003510:Cyclohexanes; D006845:Hydrocarbons, Fluorinated; D009705:Nucleosides; C121084:difluorocarbene