Total synthesis of trifluorobutyryl-modified, globally protected sialyl Lewis x by a convergent [2+2] approach

Tetrahedron Lett. 2015 Jan 1;56(1):109-114. doi: 10.1016/j.tetlet.2014.11.029.


Structural and quantitative changes in the expression of sialic acid residues on the surface of eukaryotic cells profoundly influence a broad range of biological processes including inflammation, antigen recognition, microbial attachment, and tumor metastasis. Uptake and incorporation of sialic acid analogues in mammalian cells enable structure-function studies and perturbation of specific recognition events. Our group has recently shown that a trifluorobutyryl-modified sialic acid metabolite diminishes the adhesion of mammalian cells to E and P-selectin, presumably by leading to the expression of fluorinated sLex epitopes on cell surfaces, and interfering with the sLex-selectin interactions that are well known in mediating tumor cell migration.1 For studies directed towards understanding the molecular basis of this reduced adhesion, chemical synthesis of trifluorobutyrylated sialyl Lewis x (C4F3--sLex) was crucial. We have developed a highly efficient [2+2] approach for the assembly of C4F3-sLex on a preparative scale that contains versatile protective groups allowing the glycan to be surface immobilized or solubilized as needed for biophysical studies to investigate selectin interactions. This strategy can, in principle, be used for preparation of other N-modified sLex analogues.

Keywords: cancer metastasis; cellular adhesion; convergent synthesis; fluorinated carbohydrates; glycosylation; sialic acid; sialyl Lewis X; sialylation.