Numerous biomolecules possess 2-deoxy-2-amino-alpha-D-glucosamine as structural component. However, chemical glycosylations aimed at this backbone are usually not easily attained without generating the unwanted beta-isomer. Here, we present a versatile approach in generating this important linkage in full alpha-stereoselectivity by relying on the influence of a carefully selected set of orthogonal protecting groups on 2-azido-2-deoxy-D-glucosyl donors.1 The protecting group combination enabled excellent stereoselectivity regardless of leaving group and activators, allowing the efficient generation of the core skeletons of glycosylphosphatidyl inositol anchors, heparosan, heparan sulfate, and heparin. The installed orthogonal protecting groups were successfully transformed and manipulated to further carry out the total synthesis of the irregular 3-O-sulfonated heparan sulfate octasaccharides with a alpha-methyl group at the reducing end. The activity of chemically prepared octasaccharides against the herpes simplex virus type 1 (HSV-1) viral infection in a dosage-dependent study will be discussed.2
Reference:
[1] M. M. L. Zulueta, S.-Y. Lin, Y.-T. Lin, C.-J. Huang, C.-C. Wang, C.-C. Ku, Z. Shi, C.-L. Chyan, D. Irene, L.-H. Lim, T.-I. Tsai, Y.-P. Hu, S. D. Arco, C.-H. Wong, S.-C. Hung, (2012) J. Am. Chem. Soc., 134, 8988.
[2] Y.-P. Hu, S.-Y. Lin, C.-Y. Huang, M. M. L. Zulueta, J.-Y. Liu, W. Chang, S.-C. Hung, (2011) Nat. Chem. 3, 557.
