Fluorine fluoro sugars

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-... 

Csuk and Glanzer [48] published a detailed compilation of NMR data of fluorinated carbohydrates. Two other reviews on fluoro-sugars also mention chemical characteristics and biological applications [49,50]. 

F-2-fluoro-2-deoxyglucose (2-FDG) is normally produced in places where a cyclotron is locally available. Its molecular formula is CsHn FOs with molecular weight of 181.3 daltons. 18F-2-FDG can be produced by electrophilic substitution with 18F-fluorine gas or nucleophilic displacement with 18F-fluoride ions. The radiochemical yield is low with the electrophilic substitution, so the nucleophilic displacement reaction has become the method of choice for 18F-FDG synthesis. Deoxyglucose is labeled with 18F by nucleophilic displacement reaction of an acetylated sugar derivative followed by hydrolysis (Hamacher et al, 1986). In nucleophilic substitution, a fluoride ion reacts to fluorinate the sugar derivative. A solution of 1,3,4,6-tetra-O-acetyl-2-0-trifluoromethane-sulfonyl-/ -D-mannopyranose in anhydrous acetonitrile is added to a dry residue of 18F-fluoride containing aminopolyether (Kryptofix 2.2.2) and potassium carbonate (Fig. 8.1). Kryptofix 2.2.2 is used as a catalyst to enhance the reactivity of the fluoride ions. The mixture is heated... 

Specifically-fluorinated methyl yft-glycosides of (1- 6)- -D-galacto-oligosaccharides have been synthesized by use of 3-fluoro sugar units... 

Nucleocidin. Ill (a New Structure) . Nucleocidin, an antitrypanosomal antibiotic produced by Streptomyces calvus, first isolated in 1957 and thought to be 9-(4-0-sulphamoylpentofuranosyl)adffliine (CioHuNgSO,), has now been shown to contain fluorine (revised formula CioHisNgSO,F). The new structure proposed is that of 9-(4-fluoro-S-0-sulphamoylpentofuranosyl)adenine [(1), or a stereoisomer], This compound is the first fluoro-sugar derivative to be isolated from any natural source. 

Different kinds of nucleosides (778) were prepared by condensation of compound 400 (see Section 11,3) with trimethylsilylated uracils under Lewis acid catalysis, and removal of one fluorine atom at C-2 of the sugars. Uridine 5 -(2-acetamido-2,4-dideoxy-4-fluoro-a-D-galactopyranosyl di-... 

Examples of fluorine-containing imino sugars as partial structures of PNPs have been reported. The S -deoxy-S -fluoro compound 116 ( S -F-Imucillin H, Scheme 29) was found to be a nanomolar inhibitor of human PNP (1 nM) as well as that of Plasmodium falciparum (A) 60 nM).237 2,-Deoxy-2,2 -difluoro derivative 117 ( -diF-immucillin-H ) exhibited slightly more inhibitory power against the microbial enzyme and an enhanced selectivity of more than three orders of magnitude (ATj 1.4 nM vs. 15 pM).238 Another type of inhibitor, the 3-fluoro compound 118 ( F-DADMe-immucillin-H ) was shown a potent picomolar inhibitor of the human enzyme (Kf 32 pM), with some selectivity over the Plasmodium phos-phorylase (2.6 nM), whereas the enantiomer 119 was 50- to 100-fold less active 239,240... 

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