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

TETRAHEDRON LETTERS

卷:56

Article

Akcay, Gizem¹  Ramphal, John Y.²  d'Alarcao, Marc²  Kumar, Krishna¹ 

[1] Tufts Univ, Dept Chem, Medford, MA 02155 USA

[2] San Jose State Univ, Dept Chem, San Jose, CA 95192 USA

关键词: Sialic acid;    Sialyl Lewis X;    Sialylation;    Fluorinated carbohydrates;    Cellular adhesion;    Cancer metastasis;   

DOI  :  10.1016/j.tetlet.2014.11.029

来源: Elsevier

【 摘 要 】

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 tumour 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 sLe(x) epitopes on cell surfaces, and interfering with the sLe(x)-selectin interactions that are well known in mediating tumour cell migration (J. Med. Chem. 2010, 53, 4277). For studies directed towards understanding the molecular basis of this reduced adhesion, chemical synthesis of trifluorobutyrylated sialyl Lewis X (C4F3-sLe(x)) was crucial. We have developed a highly efficient [2+2] approach for the assembly of C4F3-sLe(x) 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 sLe(x) analogues. (C) 2014 Elsevier Ltd. All rights reserved.

【 授权许可】

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