“…The third approach, which was the one we followed, involves the initial synthesis of a 2-fluoroglycal, which is then reacted with an electrophilic fluorine source such as Selectfluor, F 2 , acetylhypofluorite or trifluoroxymethane. 25,[30][31] The gem-difluoro sugars can be obtained in respectable yields in this manner. This route is also highly compatible with the synthesis of 2-deoxy-2-chloro-2-fluoro sugars, since the same fluoroglycal intermediate can be reacted with electrophilic chlorine sources.…”
Section: Introductionmentioning
confidence: 97%
“…The most common approach is to selectively oxidize the hydroxyl group at the site in question and then react the ketone with DAST to introduce the gem-difluoro functionality. [22][23][24][25] However, the success of this reaction is highly dependent on the structure of the substrate, particularly with respect to the identities and stereochemistry of neighboring groups. [26][27] In some cases yields of over 80% were obtained while in other cases, moderate yields or even no detectable yields were observed due to competing side reactions such as migrations and eliminations.…”
The synthesis of a series of 2-deoxy-2,2-dihaloglycosyl halides as potential alpha-glycosidase inactivators has been achieved via the halogenation of protected 2-fluoroglycal precursors. Direct chlorination of per-O-acetylated 2-fluoro-d-glucal and 2-fluoromaltal followed by basic deprotection yielded the corresponding 2-chloro-2-deoxy-2-fluoroglycosyl chlorides. Reaction of the per-O-acetylated 2-fluoroglycals with acetyl hypofluorite or Selectfluor yielded the 2-deoxy-2,2-difluoroglycosyl derivatives, which were converted to their alpha-chlorides using thionyl chloride and deprotected under basic conditions. Trinitrophenyl glycosides of the 2-deoxy-2,2-difluoro mono- and disaccharides were synthesized by arylation of the hemiacetals with picryl fluoride, then deprotected with HCl in methanol. All three monosaccharide derivatives caused active site-directed, time-dependent inactivation of yeast alpha-glucosidase via the trapping of covalent glycosyl-enzyme intermediates, and kinetic parameters for inactivation by each compound were determined. Surprisingly neither of the 2-deoxy-2,2-dihalomaltosyl chlorides caused time-dependent inactivation of human pancreatic alpha-amylase, despite the fact that the trinitrophenyl 2-deoxy-2,2-difluoromaltoside functioned in that mode. The trinitrophenyl glycosides appear to be approximately 1000-fold more reactive than the corresponding chlorides in the enzyme active sites.
“…The third approach, which was the one we followed, involves the initial synthesis of a 2-fluoroglycal, which is then reacted with an electrophilic fluorine source such as Selectfluor, F 2 , acetylhypofluorite or trifluoroxymethane. 25,[30][31] The gem-difluoro sugars can be obtained in respectable yields in this manner. This route is also highly compatible with the synthesis of 2-deoxy-2-chloro-2-fluoro sugars, since the same fluoroglycal intermediate can be reacted with electrophilic chlorine sources.…”
Section: Introductionmentioning
confidence: 97%
“…The most common approach is to selectively oxidize the hydroxyl group at the site in question and then react the ketone with DAST to introduce the gem-difluoro functionality. [22][23][24][25] However, the success of this reaction is highly dependent on the structure of the substrate, particularly with respect to the identities and stereochemistry of neighboring groups. [26][27] In some cases yields of over 80% were obtained while in other cases, moderate yields or even no detectable yields were observed due to competing side reactions such as migrations and eliminations.…”
The synthesis of a series of 2-deoxy-2,2-dihaloglycosyl halides as potential alpha-glycosidase inactivators has been achieved via the halogenation of protected 2-fluoroglycal precursors. Direct chlorination of per-O-acetylated 2-fluoro-d-glucal and 2-fluoromaltal followed by basic deprotection yielded the corresponding 2-chloro-2-deoxy-2-fluoroglycosyl chlorides. Reaction of the per-O-acetylated 2-fluoroglycals with acetyl hypofluorite or Selectfluor yielded the 2-deoxy-2,2-difluoroglycosyl derivatives, which were converted to their alpha-chlorides using thionyl chloride and deprotected under basic conditions. Trinitrophenyl glycosides of the 2-deoxy-2,2-difluoro mono- and disaccharides were synthesized by arylation of the hemiacetals with picryl fluoride, then deprotected with HCl in methanol. All three monosaccharide derivatives caused active site-directed, time-dependent inactivation of yeast alpha-glucosidase via the trapping of covalent glycosyl-enzyme intermediates, and kinetic parameters for inactivation by each compound were determined. Surprisingly neither of the 2-deoxy-2,2-dihalomaltosyl chlorides caused time-dependent inactivation of human pancreatic alpha-amylase, despite the fact that the trinitrophenyl 2-deoxy-2,2-difluoromaltoside functioned in that mode. The trinitrophenyl glycosides appear to be approximately 1000-fold more reactive than the corresponding chlorides in the enzyme active sites.
“…Several similar works with similar results have appeared, including fluorination of lactal and related disaccharides, which after 4 h at 0 °C formed 2-deoxy-2-fluorolactose and 2-deoxy-2-fluorodisaccharides (Scheme 21) . Various gem -difluorosugars, which frequently are biologically important, were also obtained by treating monofluoroolefinic sugars with CF 3 OF through an ionic mechanism (Scheme 22) …”
Section: The Chemistry Of Cf3ofmentioning
confidence: 69%
“…38 Various gem-difluorosugars, which frequently are biologically important, 39 were also obtained by treating monofluoroolefinic sugars with CF 3 OF through an ionic mechanism (Scheme 22). 40 Fluoroxytrifluoromethane was also used for fluorination of other biologically interesting compounds such as various pyrimidines. In 1972 Barton showed that uracil, cytosine, thymine, and others, could be directly fluorinated with CF 3 OF at temperatures from -78 to 25 °C in very good yields, using aqueous trifluoroacetic acid as a solvent.…”
“…420 The 1,2,2-trifluorinated fucosamine derivatives aand b-882 (Scheme 125) were synthesized by the Lukacs group as intermediates in their 2,2-difluorodaunosamine synthesis. 421 Starting from Dglucose, anomeric protection as a-benzyl glucoside, followed by standard benzylidene protection gave 868. In the original report, 868 was converted to 869 via the corresponding dimesylate, which gave a very low yield (2%).…”
Fluorinated carbohydrates have found many applications in the glycosciences. Typically, these contain fluorination at a single position. There are not many applications involving polyfluorinated carbohydrates, here defined as monosaccharides in which more than one carbon has at least one fluorine substituent directly attached to it, with the notable exception of their use as mechanism-9.3.1
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