Synthesis of 2-fluoro-substituted and 2,6-modified purine 2′,3′-dideoxy-2′,3′-difluoro-d-arabinofuranosyl nucleosides from d-xylose

Synthesis of phosphonate derivatives of 2′-deoxy-2′-fluorotetradialdose d-nucleosides and tetradialdose d-nucleosides

“…To avoid elimination reactions and the formation of side products during the fluorination step, it was reported that the reaction had to be performed on a precursor bearing unprotected trans diol. 10 , 11 Therefore, l -xylose glycoside 9 was treated with DAST to afford the fluorinated product in 54% yield. In agreement with the literature, 6 , 7 we observed the regioselective formation of 3-fluoro- l -ribofuranoside 10 .…”

Parameterization and Application of the General Amber Force Field to Model Fluro Substituted Furanose Moieties and Nucleosides

“…The selective introduction of fluorine or fluorine-containing functional groups to small organic molecules has proven extremely useful in modifying the physicochemical and pharmacokinetic properties of small drug molecules. [2][3][4] In the field of nucleoside and nucleotide chemistry, fluorine substitutions to the 2' and 3' positions of the sugar moiety have been shown dramatically effect both metabolic stability and biological activity. [5][6][7] This is not only due to the inherent strength of the C-F bond that is highly resistant to metabolic cleavage but also to the polarizing effect of the fluoro group that influences the sugar pucker angle through the gauche effect.…”

The Synthesis and Glycoside Formation of Polyfluorinated Carbohydrates

“…346,[385][386][387] Indeed, isolated 733 was shown to give 730 by DAST treatment in 66% yield. 346 Alternatively, activation of the OH-2 group in 733 as imidazoylsulfonate 734 allowed fluoride displacement to give 730 in 49% yield. 385 Treatment of b-732 with DAST led to the isolation of four compounds, of which 3-deoxy-3-fluoro-bribofuranoside 737 was the major, followed by 2,3-anhydro-b-ribofuranoside 736.…”

“…380 Hence, 730 was acetolyzed to give 738 (Scheme 104), which was converted to the more reactive glycosyl bromide 739, which has generally been the substrate of choice for nucleobase introductions. 346,380,385,388 For example, reaction of 739 with deprotonated purines gave good yields of the corresponding nucleoside derivatives. Using the sodium salt of 2,6dichloropurine led to a 2.9-4:1 anomeric ratio of β-to α-740, 385,388 which was improved by using the corresponding potassium salt to 9:1.…”

“…388 In contrast, reaction of 739 with the potassium salt of 2fluoroadenine led to a 1:1 anomeric ratio of 741. 346 Their deprotection then gave 742.…”