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. 2010 Jul 2;12(13):2928-31.
doi: 10.1021/ol100934z.

Synthesis and evaluation of amino-modified alpha-GalCer analogues

Matthias Trappeniers  1 , René Chofor, Sandrine Aspeslagh, Yali Li, Bruno Linclau, Dirk M Zajonc, Dirk Elewaut, Serge Van Calenbergh
Affiliations

Synthesis and evaluation of amino-modified alpha-GalCer analogues

Matthias Trappeniers et al. Org Lett. .

Abstract

Alpha-GalCer analogues featuring a phytoceramide 3- and 4-amino group have been synthesized. A Mitsunobu reaction involving phthalimide was employed for the introduction of the amino groups at the 3- and 4-positions of suitable phytosphingosine-derived precursors. The influence of these modifications on the interaction with the T-cell receptor of NKT cells was investigated, as well as the capacity of the amino-modified analogues to induce a cytokine response after in vivo administration.

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Figures

Figure 1
Figure 1
Structures of KRN7000 (1) and amino-modified analogues (2–5).
Figure 2
Figure 2
INF-γ and IL-4 secretion after intraperitoneal injection of α-GalCer (1) and 2–5 in mice (* P < 0.01 vs α-GalCer).
Scheme 1
Scheme 1
Synthesis of the 3-amino-3-deoxy-α-GalCer analogues 2 and 3
Scheme 2
Scheme 2
Synthesis of the D-ribo and L-lyxo glycosidation acceptors 22 and 23
Scheme 3
Scheme 3
Synthesis of the 4-amino-4-deoxy-α-GalCer analogues 4 and 5
See this image and copyright information in PMC

References

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