Synthesis and conformational analysis of 2'-fluoro-5-methyl-4'-thioarabinouridine (4'S-FMAU).
An improved synthesis of 2'-deoxy-2'-fluoro-5-methyl-4'-thioarabinouridine (4'S-FMAU) is described. Participation of the 3'-O-benzoyl protecting group in the thiosugar precursor influenced the stereochemistry of the N-glycosylation reaction in nonpolar solvents, permitting a higher beta/alpha ratio than previously observed for similar Lewis acid catalyzed glycosylations. Conformational analysis of the nucleoside using 3JHH and 3JHF NMR coupling constants together with the PSEUROT program showed that it adopted a predominantly northern conformation in contrast to 2'-deoxy-2'-fluoro-5-methylarabinouridine (FMAU), whose PSEUROT conformational analysis is presented here for the first time, which showed a dominantly southeast conformation. The sharp conformational switch attained by replacing the ring heteroatom is attributed to a decrease in relevant steric and stereoelectronic effects.
Watts
Jonathan K
JK
Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, QC, Canada H3A 2K6.
Sadalapure
Kashinath
K
Choubdar
Niloufar
N
Pinto
B Mario
BM
Damha
Masad J
MJ
D006031:Glycosylation; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009005:Monosaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D009705:Nucleosides / Q000737:chemistry; D014529:Uridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry
C512016:2'-fluoro-5-methyl-4'-thioarabinouridine; D009005:Monosaccharides; D009705:Nucleosides; D014529:Uridine