Synthesis of Quinamide-Based Disaccharide Mimetics

Document Type

Poster

Department

Chemistry

Conference Title

Annual Conference of the Society for Glycobiology

Organization

Society for Glycobiology

Location

San Diego, CA

Conference Dates

December 3-6, 2003

Date of Presentation

12-3-2003

Abstract

Oligosaccharides constitute important recognition motifs for fundamental biological processes such as cell-cell communication, immune response, and fertilization. Whereas most protein-carbohydrate interactions are weak, a pronounced increase in binding strength can be observed frequently if oligosaccharide clusters are involved. This “glycoside cluster effect” has been the foundation of efforts for the development of carbohydrate-based vaccines and drugs. This paper reports the synthesis and characterization of Small Cluster Oligosaccharide Mimetics (SCOM). The per-O-acetylated derivative of L-fucose was synthesized by an improved method. Tetra-O-acetyl-L-fucopyranose was converted to the glycosyl cyanide by HgBr2-promoted reaction with trimethylsilyl cyanide (Me3SiCN). Reduction of the fucosyl cyanide in the presence of t-butyloxycarbonyl anhydride (Boc)2O yielded the corresponding Boc-protected aminomethyl-C-glycoside and a disaccharidic analog. Both monomer and dimer were separated by flash column chromatography and were characterized by Nuclear Magnetic Resonance (NMR) spectroscopy and Electrospray-Ionization Mass Spectrometry (ESIMS). Removal of the acetyl groups and the Boc group towards fully deprotected aminomethyl-C-glycosides was investigated for both the C-glycoside monosaccharide and the disaccharide. The deprotected product was coupled with the previously synthesized 4,5-O-isopropylidene-1,3-lactone of quinic acid to yield the corresponding polyhydroxyl cluster qinamides. In separate experiments, the isopropylidenated quinic acid lactone was coupled with D-glucamine and with the previously synthesized benzyl-4,6-O-benzylidene-2-amino-2-deoxy-D-glucosamine to yield the corresponding quinamides. The identity of all products was confirmed by 1D-/2D-NMR spectroscopic techniques and mass spectrometry.

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