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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.The key challenge in the synthesis of the target molecules involved the stereoselective synthesis of the alpha-glycosidic linkage.Of the methods examined, the per-TMS-protected glycosyl iodide donor was completely alpha-selective, and could be scaled up to provide gram quantities of the azide precursor 11, from which a range of N-acylated alpha-L-fucosyl ceramides were readily obtained and evaluated for ex vivo expansion of human iNKT cells.

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

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(a) Me2S, 2-Cl-pyridine, Tf2O, CH2Cl2; (b) dimethyl(methylthio)sulfonium triflate (DMTST), CH2Cl2, 0 °C-rt.
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fig2: (a) Me2S, 2-Cl-pyridine, Tf2O, CH2Cl2; (b) dimethyl(methylthio)sulfonium triflate (DMTST), CH2Cl2, 0 °C-rt.

Mentions: Fan et al.25 reported the synthesis of compound 4d, while Okamoto et al.27 reported that of compound 4e. Both groups obtained their target compounds as an α, β mixture (3:1 ratio) from different glycosyl donors and acceptors (Scheme 1). On the other hand, in the original reported synthesis of the fucosylceramide 1, only the α-anomer was isolated when another ceramide acceptor was used under different reaction conditions.


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) Me2S, 2-Cl-pyridine, Tf2O, CH2Cl2; (b) dimethyl(methylthio)sulfonium triflate (DMTST), CH2Cl2, 0 °C-rt.
© Copyright Policy
Related In: Results  -  Collection

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

fig2: (a) Me2S, 2-Cl-pyridine, Tf2O, CH2Cl2; (b) dimethyl(methylthio)sulfonium triflate (DMTST), CH2Cl2, 0 °C-rt.
Mentions: Fan et al.25 reported the synthesis of compound 4d, while Okamoto et al.27 reported that of compound 4e. Both groups obtained their target compounds as an α, β mixture (3:1 ratio) from different glycosyl donors and acceptors (Scheme 1). On the other hand, in the original reported synthesis of the fucosylceramide 1, only the α-anomer was isolated when another ceramide acceptor was used under different reaction conditions.

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.The key challenge in the synthesis of the target molecules involved the stereoselective synthesis of the alpha-glycosidic linkage.Of the methods examined, the per-TMS-protected glycosyl iodide donor was completely alpha-selective, and could be scaled up to provide gram quantities of the azide precursor 11, from which a range of N-acylated alpha-L-fucosyl ceramides were readily obtained and evaluated for ex vivo expansion of human iNKT cells.

View Article: PubMed Central - PubMed

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

Show MeSH
Related in: MedlinePlus