Synthesis and biological activity of alpha-L-fucosyl ceramides, analogues of the potent agonist, alpha-D-galactosyl ceramide KRN7000.
Bottom Line: Activation of iNKT cells is known to lead to the production of cytokines that can help alleviate or exacerbate these conditions. alpha-Galactosyl ceramide (alpha-GalCer) is a known agonist of iNKT cells and it is believed that its fucosyl counterpart might have similar immunogenic properties.We herein report the synthesis of alpha-L-fucosyl ceramide derivatives and describe their biological evaluation.The key challenge in the synthesis of the target molecules involved the stereoselective synthesis of the alpha-glycosidic linkage.
Affiliation: School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.Show MeSH
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Mentions: The per-O-trimethylsilyl-α-l-fucosylpyranosyl iodide 10 was generated by the reaction of the per-O-tetramethylsilyl-α-l-fucose with one equivalent of iodotrimethylsilane35 and then added to the phytosphingosine acceptor 7 which was premixed with diisopropylethylamine (DIPEA) and TBAI (Scheme 3). After 2 days at room temperature, the solvent was evaporated and the TMS protecting groups were removed by treatment with an acidic resin in MeOH. Compound 11 was obtained as the α-anomer exclusively in an overall yield of 62%. The formation of the desired α-linkage was confirmed by the H-1 and C-1 signals in 1H and 13C NMR. Methanolysis, followed by hydrogenation of the azide then afforded compound 9.
Affiliation: School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.