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Synthesis and biological activity of alpha-L-fucosyl ceramides, analogues of the potent agonist, alpha-D-galactosyl ceramide KRN7000.

Veerapen N, Reddington F, Bricard G, Porcelli SA, Besra GS - Bioorg. Med. Chem. Lett. (2010)

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.

View Article: PubMed Central - PubMed

Affiliation: School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.

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Related in: MedlinePlus

(a) TBAI, DIPEA, CH2Cl2, rt; (b) Dowex 50WX8-200, MeOH, rt, 62% over two steps; (c) NaOMe/MeOH, quantitative; (d) H2, Pd, MeOH, 80%; (e) C25H51COCl or C23H47COC1, THF, NaOAc, 78–80%.
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fig4: (a) TBAI, DIPEA, CH2Cl2, rt; (b) Dowex 50WX8-200, MeOH, rt, 62% over two steps; (c) NaOMe/MeOH, quantitative; (d) H2, Pd, MeOH, 80%; (e) C25H51COCl or C23H47COC1, THF, NaOAc, 78–80%.

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.


Synthesis and biological activity of alpha-L-fucosyl ceramides, analogues of the potent agonist, alpha-D-galactosyl ceramide KRN7000.

Veerapen N, Reddington F, Bricard G, Porcelli SA, Besra GS - Bioorg. Med. Chem. Lett. (2010)

(a) TBAI, DIPEA, CH2Cl2, rt; (b) Dowex 50WX8-200, MeOH, rt, 62% over two steps; (c) NaOMe/MeOH, quantitative; (d) H2, Pd, MeOH, 80%; (e) C25H51COCl or C23H47COC1, THF, NaOAc, 78–80%.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2957807&req=5

fig4: (a) TBAI, DIPEA, CH2Cl2, rt; (b) Dowex 50WX8-200, MeOH, rt, 62% over two steps; (c) NaOMe/MeOH, quantitative; (d) H2, Pd, MeOH, 80%; (e) C25H51COCl or C23H47COC1, THF, NaOAc, 78–80%.
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.

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.

View Article: PubMed Central - PubMed

Affiliation: School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.

Show MeSH
Related in: MedlinePlus