Deoxyfluoro sugars

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... 

Several simple deoxyfluoro sugars and glycosyl fluorides were utilized " as probes for hydrogen bonding in the glycogen phosphorylase-o-glucose complex. 

Reactions that have led to other deoxyhalogeno sugars do not necessarily lead to deoxyfluoro sugars, as, for example, in the attempted decomposition of fluoroformates, the treatment of diazoketones and of 2-deoxy-2-diazohexonates with hydrogen fluoride, and the reaction of benzoxonium ions with halide ions. The reaction2281229 by which fluoroformates are thermally or catalytically decarbonylated to give alkyl fluorides has been applied to carbohydrates. Both thermal and catalytic treatment of 6-0-(fluoroformyl)-l,2 3,4-di-0-isopropylidene-... 

New Synthetic Methods Emphasizing Deoxyfluoro Sugars and Protective-Group Strategy... 

The search for new methods of synthesis of halogenated carbohydrates continues to be an active area of investigation. The compounds are of utility as synthetic intermediates, and many of them are of intrinsic value in biochemistry and pharmacology. In the present Chapter methods for the synthesis of deoxyfluoro sugars and glycosyl fluorides are discussed. 

The first published deoxyfluoro derivative of an imino sugar was Vogel s... 

From the available items of information, it can be concluded that deoxyfluoro derivatives of imino sugars and relatives are valuable tools for characterization of glycosidases as they pertain to the significance of individual functional groups around the ring, as well as considerations concerning the pH dependency of glycosidase and inhibitor activity. Their potential as leads toward pH-dependent, selective inhibitors has yet, however, to be realized in particular applications. 

The nucleophile for which increased reactivity is most critical is the fluoride ion [3,4], Water molecules bind tightly to this ion, and their presence dramatically reduces its effective nucleophilicity. A variety of fluoride ion sources have been used in an effort to improve product yields in deoxyfluoro sugar synthesis [26,34]. The yields of substitution and elimination products generated from reactions with fluoride ion from several sources are listed in Table 2 [26]. Currently, the most attractive source of fluoride ion is tris(dimethylanuno)-5ulfur (trimetbylsilyl)difluoride (TASF), which is soluble in a variety of oiganic solvents and produces an anhydrous fluoride ion [33]. 

B. Doboszewski, G. W. Hay, and W. A. Szarek, The rapid synthesis of deoxyfluoro sugars using tris(diinethylamim)8ulfoiiiuin difliiorotrimethylsihcate (TASP), Con. J. Chem. 65 412 (1987). 

Deoxyfluoro sugars.3 Carbohydrate triflates are converted into deoxyfluor-ides by reaction with TASF (3 equiv.) in CH2C12 (0 — 20°, 10 min.) in 65-70% yield. 

The above-discussed methods are mainly used for the synthesis of chloro, bromo and iodo sugars. A different approach has to be taken when a deoxyfluoro sugar derivative is required, and the most commonly applied reagent for direct fluorination is diethylaminosulfur trifluoride... 

Foster, A B, Hems, R, Deoxyfluoro sugars via displacement of sulfonyloxy groups with tetrabutylammonium fluoride. Methods Carbohydr. Chem., 6, 197-200, 1972. 

The first preparation of a secondary deoxyfluoro sugar, other than by total synthesis, involved the cleavage of 2,2 -anhydro-3-( 8-D-arabino-furanosyl) uracil (3) to give 3-(2-deoxy-2-fluoro-/3-D-ribosyl) uracil. This reaction, which can be extended to cleavage by hydrogen bromide or chloride, is at pr ent the only route to 2-deoxy-2-fluoro-D-ribose deriva-... 

---