Synthesis of a biotinylated keratan sulfate tetrasaccharide composed of dimeric Galβ1-4GlcNAc6Sβ. (27th November 2017)

• Record Type: Journal Article
• Authors: Takeda-Okuda, Naoko; Yamaguchi, Yoshiki; Uzawa, Jun; Tamura, Jun-ichi
• Is Part Of: Carbohydrate research. Volume 452(2017)
• Page Start: 97
• Page End: 107
• Publication Date: 2017-11-27
• Subjects: Keratan sulfate -- Glycosylation -- Oligosaccharide; All allyl -- Bn benzyl -- Z benzyloxycarbonyl -- TBDPS tert-butyldiphenylsilyl -- GlcN D-glucosamine -- Gal D-galactose -- GAG glycosaminoglycan -- KS keratan sulfate -- MS molecular sieves -- Np 2-naphthyl -- NAP 2-naphthylmethyl -- NIS N-iodosuccinimide -- Phth phthal -- AgOTf silver trifluoromethanesulfonate -- TMSOTf trimethylsilyl trifluoromethanesulfonate -- TfOH trifluoromethanesulfonic acid; Carbohydrates -- Periodicals; Chemistry, Organic -- Periodicals; Biochemistry -- Periodicals; Carbohydrates -- Periodicals; Chimie organique -- Périodiques; Glucides -- Périodiques; Biochemistry; Carbohydrates; Chemistry, Organic; Periodicals; Electronic journals; 507.78
• DOI: 10.1016/j.carres.2017.09.005
• Languages: English
• ISSNs: 0008-6215

Abstract

Abstract: We successfully synthesized the biotinylated keratan sulfate tetrasaccharide, Galβ1-4GlcNAc6Sβ1-3Galβ1-4GlcNAc6Sβ in a stereocontrolled manner. The suitably protected Galβ1-4GlcNPhth unit was converted to the corresponding donor and acceptor. Optimization in 2 + 2 coupling using AgOTf, CuBr2, and n -Bu4 NBr in CH3 NO2 at a low temperature afforded the desired tetrasaccharide that suppressed glycal formation. The subsequent chemoselective removal of the protecting group at O -6 of two GlcNAcs, sulfation, and deprotection procedures as well as biotinylation gave the target compound. Graphical abstract: We achieved the stereocontrolled synthesis of keratan sulfate tetrasaccharide; Galβ1-4GlcNAc6Sβ1-3Galβ1-4GlcNAc6Sβ having sulfate groups at both 6-OH of two GlcNAc residues and linking to biotin via hydrophilic linker. Highlights: Galβ1-4GlcNAc6Sβ1-3Galβ1-4GlcNAc6Sβ was synthesized in a stereocontrolled manner. Optimized 2 + 2 coupling afforded the tetrasaccharide suppressing glycal formation. Glycosylation was regioselectively achieved with the triol acceptor of Gal at O-3.