Fluorinated sugar analogues

Regioselective opening of 2 ,3 -/yxo-epoxides with a lithiated dithian gave rise to branched structures of type (63, B=U or T) which could be converted (Scheme 9) into 3 -C-difluoromethyl compounds (64) and thence into analogues (65) with an additional fluorine atom at C-2 . 22 Alternatively, intermediates (63) could be used as precursors for 3 -C-hydroxymethyl systems (66), 23 and, by successive fluorination, fluoromethyl analogues of types (67) and (68) were obtained. 22 jn a synthesis of 3 -deoxy-3 -hydroxymethyl adenosine (69), the branched-chain sugar derivative (70),... 

The recent synthesis of fluorinated analogues of eldolide, which is a sexual pheromone of a devastating insect of sugar cane has been achieved in studies on... 

In this chapter, fluorinated saccharidic compounds are considered in the following order fluorinated analogues of furanoses and nucleosides, followed by pyranoses and then fluoromethylated sugars. Finally, a brief summary of perfluoroalkylated sugars and of their amphiphilic properties is given. 

MONO- AND DIFLUORINATED ANALOGUES OF SUGARS 6.2.1 Fluorinated Furanoses and Nucleosides... 

Inhibition of Chorismate Synthase Shikimic and quinic acids are used by microorganisms, fungi, and superior plants for the synthesis of essential aromatic amino acids from acyclic sugars. Fluorinated analogues of substrates and reaction intermediates have been synthesized in order to inhibit enzymes involved in... 

Fluorinated analogues of nucleosides are drugs that interact with enzymes involved in the synthesis of DNA and RNA (cf. Chapter 7). They are developed for treatment of cancer and viral infections. Fluorine atoms can be present either on the base moiety or on the sugar one. 

Deoxy-2 -fluoro-4 -thio-L-ara/)z o-nucleosidcs 195 were synthesized starting from D-xylose via the 4-tluo-i,-arabinitol derivative 151 as a key intermediate (Scheme 54). Introduction of fluorine at C-2 of 151 with DAST yielded 193, which was transformed into tliio sugar 194 by oxidation and Pummerer rearrangement. Coupling of 194 witli the base and debenzylation afforded 195. The thymine analogue exhibited a moderate activity against both HSV-1 and HSV-2. 

There are a number of reasons why these analogues are useful. Firstly the substitution of a sugar hydroxyl by a fluorine or by hydrogen is sterlcally conservative since both these substituents are smaller than the original hydroxyl. Table I provides the relevant... 

Many studies have been performed on fluorinated anthraqrclines and their comparison with non-fluorinated analogues allow a better and deeper knowledge of the biological mechanisms involved in the activity of this class of drugs. We now know the influence of this small electrophilic atom, when introduced on different positions of the aglycone and sugar moiety. 

None of these compounds were inhibitors of tubulin polymerisation. This was obviously attributed to the presence of the bulky sugar on the double bond. Our developed methodology allowed the synthesis of the unknown simplified compounds 11. Even these compounds failed to inhibit tubulin polymerisation whereas some fluorinated analogues (F instead of CH2OH in 11) or ethoxy substituted ones (OEt instead of CH2OH in 11) did. Nevertheless some of compounds 10 were found to have antiproliferative properties in the submicromolar range against different cancer cell lines by a yet unknown mechanism. ... 

When the A-tosylaziridine 11 was opened with fluoride (KHFj, DMF, 150°C) initially the 2-fluoride 12 was produced, but over time the thermodynamic product 13 formed, presumably by reversal back to 11. This reaction was also utilized in the synthesis of fluorinated kanamycin derivatives." These and other syntheses of 4 -deoxy-4 -fluorokanamycins A and B are covered in Chapter 19. The synthesis of a fluorinated analogue of the acceptor of bovine (l- 4)-P-D-galactosyl transferase is mentioned in Chapter 3, and the conformational analysis of some deoxyfluoro sugars by H-n.m.r. spectroscopy is detailed in Chapter 21. The use of e.i. and c.i. mass spectrometry to determine the location of a fluorine atom in deoxyfluoro glucosides is outlined in Chapter 22. 

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