Glycolipids which are structurally related to KRN7000 and produced by Sphingomonas bacteria play an important role as antigens for natural killer T (NKT) cells to release cytokines.1 Stimulation of NKT cells is achieved via presentation of glycolipids by the glycoprotein CD1d.2 A limited number of glycolipids have been identified to stimulate NKT cells. Thus, novel strategies for the synthesis of new glycolipids antigens have been developed. Structural modifications include: Substitution and variation of the sugar, modification of the polar moiety of the ceramide, the lipid chain and the nature and configuration of the glycosidic bond.
Presented here are the syntheses of both 1,4- and 1,5-α-triazole glycolipids based on galactose and galacturonic acid.3 Key steps include chelation induced anomerisation to provide the α-azide precursor and copper azide-alkyne cycloaddition (CuAAC) and ruthenium azide-alkyne cycloaddation (RuAAC) to achieve the desired triazoles.
References:
1. (a) Mattner, J.; DeBord, K. L.; Ismail, N.; Goff, R. D.; Cantu, C.; Zhou, D.; Saint-Mezard, P.;Wang, V.; Gao, Y.;Hoebe, K.; Schneewind, O.; Walker, D.; Beutler, B.; Teyton, L.; Savage, P.; Bendelac, A. Nature 2005, 434, 525–529. (b) Kinjo, Y.; Wu, D.; Kim, G.; Xing, G.-W.; Poles, M. A.; Ho, D. D.; Tsuji, M.; Kawahara, K.; Wong, C.-H.; Kronenberg, M. Nature 2005, 434, 520–525.
2. Kobayashi, E.;Motoki, K.;Uchida, T.; Fukushima,H.; Koezuka, Y. Oncol. Res. 1995, 7, 529–534.
3. O’Reilly, C.; Murphy, P. V. Org. Lett. 2011, 13, 5168-5171.
