459170-27-5Relevant academic research and scientific papers
Fluoridolysis of 5,6-epoxy carbohydrates: application to the synthesis of 5-fluoro lactosamine and isolactosamine glycosides
Hagena, Tara L.,Coward, James K.
body text, p. 781 - 794 (2009/10/10)
The synthesis of 6-selenophenyl derivatives of β-1,3 and β-1,4 disaccharides has been explored for the purpose of extending our epoxide fluoridolysis methodology to the synthesis of 5-fluoro analogues of N-acetyl isolactosamine (isoLacNAc, lacto-N-biose) and N-acetyl lactosamine (LacNAc) glycosides. Successful synthesis of the C-6 selenium-containing disaccharides was achieved via Lewis acid-mediated donor and acceptor substrates, the latter containing a selectively protected C-6 hydroxyl group for ultimate conversion to the desired 6-selenophenyl disaccharides. In contrast, the use of selenium-containing acceptor substrates under a variety of conditions failed to yield the desired selenium-containing disaccharides. Oxidation of the 6-selenophenyl derivatives to the corresponding selenoxides followed by thermal elimination yielded the exocyclic olefins, which were converted to the 5,6-epoxides. Epoxide fluoridolysis yielded the desired target compounds, 5-fluoro β-octyl glycoside analogues of type 1 and type 2 glycans. The newly synthesized fluorine-containing disaccharides have potential application as fucosyltransferase substrates, both for mechanistic studies and in the chemoenzymatic synthesis of fluorine-containing oligosaccharides.
Synthesis of 5-fluoro N-acetylglucosamine glycosides and pyrophosphates via epoxide fluoridolysis: Versatile reagents for the study of glycoconjugate biochemistry
Hartman, Matthew C. T.,Coward, James K.
, p. 10036 - 10053 (2007/10/03)
Numerous carbohydrate-processing enzymes facilitate catalysis via stabilization of positive charges on or near the C-1, C-4, C-5, or C-6 positions. Substrate analogues differing only in the substitution of a fluorine for the axial C-5 hydrogen would possess reduced electron density at these positions and could be useful mechanistic probes of these enzymes. Introduction of this 5-fluoro substituent after radical halogenation was problematic because of the incompatibility of many protecting groups to the radical halogenation and the instability of the subsequent 5-fluoro hexosamines. Thus, to allow easy access to a wide variety of 5-fluoro glycosides and glycosyl phosphates, a versatile method for the introduction of the 5-fluoro group has been developed, the key step being the fluoridolysis of C-5, 6 epoxides. By use of this method, two fluorinated carbohydrates, uridine 5′-diphospho-5-fluoro-N-acetylglucosamine and octyl 5-fluoro-N-acetylglucosamine, have been synthesized. Initial biochemical investigations of these compounds show that 5-fluoro analogues are useful probes of transition-state charge development in several enzyme-catalyzed reactions.
