3 -Deoxy-3 -fluoro-3-

Cyclic sulfates rapidly react with the fluoride ion sources to give monofluoro derivatives Thus, the 2,3-cyclic sulfate of methyl-4 6 O benzylidene p D manno pyranoside cleanly reacts with tetramethylammonium fluoride to give methyl 4,6-0-benzylidene 2 deoxy 2 fluoro-p-D-glucopyranoside-3-sulfate Acid hydrolysis followed by acetylation gives 2 deoxy 2 fluoro-P-D-glucopyranoside triacetate in 84% isolated yield [5S] (equation 38)... 

Conversion of l,6-anhydro-4-0-benzyl-2 deoxy 2-fluoro-p-D-glucopyranose to the corresponding oxo derivative is earned out by ruthenium tetroxide generated in situ from ruthenium dioxide [54] (equation 49)... 

In 2003 LJngstrOm and Samuelsson described the synthesis of a radiopharmaceutical for PET (positron emission tomography) using a microwave-assisted Stille reaction [25]. l-(2 -Deoxy-2 -fluoro- 6-D-arabinofuranosyl)-... 

Methyl- C]thymine ([ C]FMAU) could be obtained in modest radiochemical yields via cross-coupling of [ CJmethyl iodide with l-(2 -deoxy-2 -fluoro-/3-D-arabinofuranosyl)-5-(trimethylstannyl)uracil. Optimal power was found to be 70W, since an increase to 100 W as well as a decrease to SOW resulted in lower radiochemical yields (Scheme 6). 

Murakami E, Bao H, Ramesh M, McBrayer TR, Whitaker T, Micolochick Steuer HM, Schinazi RF, Stuyver LJ, Obikhod A, Otto MJ, Furman PA (2007) Mechanism of activation of beta-D-2 -deoxy-2 -fluoro-2-c-methylcytidine and inhibition of hepatitis C vims NS5B RNA polymerase. Antimicrob Agents Chemother 51 503-509... 

Stuyver LJ, McBrayer TR, Tharnish PM, Clark J, Hollecker L, Lostia S, Nachman T, Grier J, Bennett MA, Xie MY, Schinazi RF, Morrey JD, Inlander JL, Furman PA, Otto MJ (2006a) Inhibition of hepatitis C replicon RNA synthesis by beta-D-2 -deoxy-2 -fluoro-2 -C-methylcytidine a specific inhibitor of hepatitis C virus replication, Antivir Chem Chemother 17 79-87... 

PSI-6130, upon phosphorylation to its 5 -triphosphate, is incorporated (as PSl-6130-MP) as a nonobligate chain terminator (Murakami et al. 2008) into RNA catalyzed by purified RNA-dependent RNA polymerase (NS5B). PSl-6130 is metabolized intracellularly to the 5 -triphosphate of p-D-2 -deoxy-2 -fluoro-2 -C-methyluridine (PSI-6206) (Ma et al. 2007), but, as compared to the 5 -triphosphate of PSI-6130, the 5 -triphosphate of PSI-6206 is less efficient an inhibitor of HCV RNA-dependent RNA polymerase than PSI-6130 5 -triphosphate (Murakami et al. 2007). 

Benzoyl-6-deoxy-3-0-methyl-2-0-triflyl-a- (183) and -)8-L-glu-copyranosyl fluorides (184) afforded on treatment with BU4NF or CsF, 2-deoxy-2-fluoro-L-ma o derivatives, 185 (75%) and 186 (55%), respectively. 

MHCl, refl. 30 min) gave 2-deoxy-2-fluoro-o-galactose (2DFGal, 86%). The crystal structure of l,3,4,6-tetra-0-acetyl-2-deoxy-2-fluoro-)9-D-galactopyr-anose has been reported. ... 

Trideoxy-2,3,4-trifluoro-D-galacto- and -gluco-pyranosyl derivatives 391 and 392 have been prepared from l,6-anhydro-4-(9-benzyl-2-deoxy-2-fluoro-/ -D-glucopyranose (385) by use of DAST, through several intermediates, as shown [385 386,10% 387- 388,72% 389 390,90% refl. toluene (for 385) or dichloromethane (for 387 and 389), 24 h]. 

D-allopyranoside (421) was treated similarly (KHFj, ethylene glycol, 160°, 4 h), the 3-fluoro-D- /wco derivative 422 (42%) was obtained mainly, contrary to the Fiirst-Plattner rule, together with the 2-deoxy-2-fluoro-D-a/rro derivative 423 (17%). 

In 1969, Adamson, Foster, and others - reported the synthesis of 2-deoxy-2-fluoro sugars by addition ofCFjOF (in CFCI3, — 80°) to 3,4,6-tri-O-acetyl-l,5-anhydro-2-deoxy-D-flra/)/>zo-hex-l-enitol (61 3,4,6-tri-O-acetyl-D-glucal). The reagent fluorinates 61 electrophilically - °° at C-2, to afford c/v-addition products trifluoromethyl 3,4,6-tri-C)-acetyl-2-deoxy-2-... 

Deoxy-3-fluoro-D-glucose (25%) and -mannose (40%) were prepared from 2-deoxy-2-fluoro-D-arabinose by a chain-extension reaction (cyanohydrin synthesis). Likewise, 4-deoxy-4-fluoro-D-glucose ° (27%) and -mannose (45%) were prepared from 3-deoxy-3-fluoro-D-arabinose. ... 

Coe and Bessell and coworkers studied the metabolic fates of 2-deoxy-2-fluoro-D-glucose (2DFG) and related compounds by using yeast hexokinase (as a model for mammalian hexokinase), and determined the kinetic constants K and V ) of the Michaelis-Menten equation D-glucose 0.17 (K in mAf)> 1 00 (relative value, D-glucose taken as 1) 2DG 0.59 0.11, 0.85 2DFG 0.19 0.03, 0.50 2-deoxy-2-fluoro-D-mannose (2DFM) 0.41 0.05, 0.85 2-deoxy-2,2-difluoro-D-nraZ>//Jo-hexose... 

Several 1 -phosphates of deoxyfluoro sugars were prepared, and their acid-catalyzed hydrolysis was studied. 2-Deoxy-2-fluoro- (580), 3-deoxy-3-fluoro- (582), 4-deoxy-4-fluoro- (583), and 6-deoxy-6-fluoro-a-D-gluco-pyranosyl phosphates (584) were prepared by treatment of the corresponding per-( -acetylated )9-D-glucopyranoses with phosphoric acid [the p anomer (581) of 580 was prepared by a different method]. The first and second ionization constants (pA a, and pA a2) of these compounds were determined potentiometrically, as well as by the F-n.m.r. chemical shifts at a series of pH values, and then the rate constants of hydrolysis for neutral (B) and monoanion (C) were decided. The first-order rate-constants (k) for 580-584 and a-D-glucopyranosyl phosphate (in Af HCIO4,25 °) were 0.068, 0.175, 0.480, 0.270, 1.12, and 4.10 (all as x lOVs), respectively. The rate... 

The incorporation and metabolism of 2-deoxy-2-fluoro-D-[ H]glucose and -D-[ H]mannose in yeast and chick-embryo cells has been studied. 2-Deoxy-2-fluoro-D-glucose, 2-deoxy-2-fluoro-D-mannose, and their GDP and UDP derivatives were found to interfere with protein (involving that of... 

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