Fluoro sugar

UDP-6-Deoxy-6-fluoro-D-galactose has been synthesized and then used as a donor substrate with a p-(l- 4)-galactosyltransferase and iV-acetylglucosamine to give 6 -deoxy-6 -fluoro-7V-acetyllactosamine. 5-Azido-3,5,6-trideoxy-3,6-di-fluoro-D-glucose has been prepared and was converted by hydrogenolysis into 

6- trideoxy-3,6-difluoronojirimycin. Sucrose has been converted via the r,2,3,3, 4, 6,6 -heptapivalate into 4-deoxy-4-fluoro-sucrose and D-ribono-1,4-lactone has been transformed into l-0-acetyl-5-0-/er/-butyldiphenylsilyl-2,3-dideoxy-2-fluoro-D-ribose and hence into nucleoside analogues. Some other deoxyfluoro nucleoside analogues are covered in Chapter 20, and the synthesis of a number of deoxyfluoro-inositols is mentioned in Chapter 18. 

A number of 2,6-dideoxy-6,6,6-trifluorohexoses were prepared from a six-carbon acetylenic precursor via selective hydroxylation of the derived alkene diastereomers, and differences in stereoselectivity of reduction of a trifluoro-methyl ketone compared with the corresponding methyl ketone are outlined in Chapter 18. Oxidation of methyl 5-0-benzyl-3(2)-deoxy-3(2)-fluoro-a-D-pento-furanosides (DMSO/TFAA) was accompanied by epimerization at the fluori-nated carbon atom a- to the ketone resulting in formation of the corresponding 2-(or 3-) keto derivatives as mixtures of two epimers. Reduction then afforded various mixtures of 2- and 3- fluoro compounds.  

The effect of K2CO3, KHCO3 and KF on the base-mediated decomposition of 

6- tetra-0-acetyl-2-0-triflyl-P-D-mannopyranose during the synthesis of 2- 

2 Chloro-, Bromo- and lodo-sugars. - The preparation of glycosyl halides and their use in the solid-phase synthesis of oligosaccharides has been reviewed/ A new method for the preparation of glycosyl chlorides involves the treatment of otherwise protected free sugars with triphosgene in the presence of pyridine/  

Carbohydrate Chemistry, Volume 34 The Royal Society of Chemistry, 2003 

Beuthien-Baumann, K. Hamacher, F. Oberdorfer and J. Steinbach, Carbohydr. Res., 2000,327,107. 

Novo and G. Resnati, Enantiocontrolled Synth. Fluoro-Org. Compd., 1999, 349 Chem. Abstr., 2000,132,166 394). 

Borrachero, F. Gabrera-Escribano, A.T. Carmona and M. Gomez-Guillen, Tetrahedron Asymmetry, 2000,11,2927. 

A review on the synthesis of gew-difluoromethylene compounds has described carbohydrate (including nucleoside) examples. The synthesis of acetylated glycosyl fluorides directly from the unprotected methyl glycosides has been effected as the first step of a GLC analytical method. First the glycoside is treated with HF followed by the addition of acetic anhydride. Full details (cf. Vol. 25, p.l05) on the preparation of glycosyl fluorides by reaction of aryl 1-thioglycosides with 4-difluoroiodotoluene have been described.  

The synthesis of 3,4-di-0-acetyl-2,6-dideoxy-6,6,6-trifluoro-a-L-/yxo-hexopyra-nosyl bromide from D-lyxose features the use of timethylsilyltrifluoromethane in the presence of fluoride ion to effect the addition of the trifluoromethyl group to an aldehyde. Similar methodology has been utilized in the synthesis of 5-deoxy-5,5,5-trifluoro-D-lyxose, -L-ribose, -L-arabinose and -D-xylose. A symposium report has looked at synthetic routes to 6-deoxy-6,6,6-trifluorosugars and the synthesis of racemic 3-deoxy-2-C-trifluoromethyI-er //tro and -threo -pentofura-noses is covered in Chapter 14. 

L-Xylose has been converted into a 2-deoxy-2-fluoro-P-L-arabinofuranose derivative, by way of a fluoride ion displacement of an imidazolylsulfonate, and then into a range of pyrimidine nucleosides. Displacement of another imidazolylsulfonate with Et3N.3HF initially formed the corresponding sulfonyl fluoride which was subsequently displaced by fluoride ion. Methyl 2,3-dideoxy-3-fluoro-5-0-(4-methylbenzoyl)-a-D-ribofuranoside, an intermediate for the syntheses of some anti-HIV nucleosides, has been synthesized from 2-deoxy-D-ribose in five steps and in 24% yield.  

Some difluoromethylene phosphonates have been prepared by phosphonyl radical addition to difluoroenol ethers, e.g. 11 gave 12. Treatment of unsaturated 1,6-anhydro sugar 13 with DAST has afforded 14, and the epoxide 15 was opened (KHF2, ethylene glycol) to give deoxyfluoro sugar 16. 

The preparation and reactions of glycosyl fluorides have been reviewed.  

3f5-Tri-O-benzyl-D-ribofuranosyl fluoride has been synthesized by the reaction of 2,3 5-tri-O-benzyl-D-ribofuranose with an adduct of diethylamine and hexafluoropropene in dichloromethane. The reaction, conducted under nitrogen,was complete in four hours at room temperature and yielded 21.4% -fluoride and 63 8% / -fluoride. The glycosyl fluorides are useful intermediates which can be reacted to produce 0- or C-glycosides. Thus a mixture of the anomeric protected ribosyl fluorides reacted with the TMS derivative of vinyl alcohol with boron trifluoride etherate catalyst to yield 90 - 95% of the p -ribofuranosyl acetone (1) only traces of the -anomer were present. 

Hexabenzyl-yS-D-ribofuranosyl-/3-D-ribofuranoside was obtained by reaction of 2,3,5-tri-O-benzyl-D-ribofuranose, or its 1-trimethylsilyl derivative, with the corresponding/9-glycosyl fluoride. Per-0-benzylated ot- and /S-gluco-, yS-galacto-, and -xylo-pyranosyl fluorides have been prepared from the corresponding per-O-acetylated fluorides in 17 - 34% yield by phase-transfer catalyzed benzyl-ation. 

Attempts to prepare 2-fluorodeoxy derivatives from the free 2-hydroxy compounds using the DAST procedure have resulted in glycosyl 

D-glucal in water gave a mixture of the fluoro-derivatives (17), 

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In this article, a treatment of n.m.r. studies on fluoro sugars is omitted, because fundamental studies in this field had already been described, and... 

Syntheses of 3-deoxy-3-fluoro sugars are described next. A rapid synthesis aimed at 3-deoxy-3-[ F]fluoro-D-glucose ( F-3DFG) was developed. ... 

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-... 

H- and F-N.m.r. Data for Aminodideoxy-3(or 4)-fluoro Sugars (and Their N-Containing... 

SZAREK Deoj fluoro Sugars and Protective-Group Strategy... 

The mechanism of inhibition of glycosylation of protein by FMan has not yet been investigated in detail however, the result that residual glycosylation of protein, noted in the presence of FGlc, does not occur in the presence of FMan indicates a different inhibitory mechanism.282 Nucleotide esters of fluoro sugars have not yet been synthesized in sufficient amount to permit testing this idea. 

Several fluoro sugars are incorporated into glycoconjugates, and therefore probably compete with the nonfluorinated sugars. Thus, 6-FGal preferentially inhibits Gal incorporation234,306 6-F-Fuc and 2-F-Fuc, the incorporation of L-fucose234,307 and 2-deoxy-2-(fluoroaceta-... 

The 6-fluoro derivatives of Gal and Fuc do not decrease the pools of ribonucleotides, nor do they inhibit protein synthesis.234,304 Interestingly, when present in low concentrations, most fluoro sugars do not give cytotoxic effects.304,313 When the size of the halogen atom is increased (Cl — Br — I derivatives), incorporation of L-fucose is lessened, and, for as-yet-unknown reasons, a concomitant increase in cytotoxicity was noted.304... 

Another interesting use of the imidazylate gr up in the furanoside series has been described by Tann et al. [89]. Thus, treatment of the C-2 imidazylate ester of the a-D-ribofuranoside tribenzoate derivative with KHF2 and HF, at 160°C, led to the 2-deoxy-2-fluoro sugar in 63% yield, presumably through the intermediacy of the fluorosulfate ester (HPLC). The 2-fluoro compound is a key intermediate in the preparation of 2 -fluoro-2 -deoxy D-arabinofuranosyl pyrimidine nucleosides, which exhibit powerful antiherpetic activity [89] (Scheme 12). 

As Laurie s work on fluoro sugars came to an end, he moved into new areas. With Ian Armitage, A. G. Marshall, and others, he systematically studied the application... 

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