A Convenient and Efficient Synthesis of SLeX Analogs

Abstract

Described is the preparation and use of tetrasaccharide 1, which enables a rapid and preparative scale synthesis of sialyl Lewis X (SLeX) analogs having 1-O- and 2-N-disubstituted glucosamine (GlcN) moieties. Such modifications should bring a dramatic change of the physical and pharmacological properties of the SLeX analogs. Therefore, tetrasaccharide 1 is a convenient intermediate for the synthesis of various SLeX analogs, since it has convertible 2-(trimethylsilyl)ethyl (SE) glycoside and the free amino group on GlcN moiety. The intermediate 1 was constructed from a glucosamine derivative by a highly efficient combined use of enzymatic galactosylation/sialylation and chemical fucosylation. Thus obtained 1 was converted into SLeX analogs by N-substitution followed by transformation of SE glycoside into other glycosides and deprotection. These synthesized analogs were found to inhibit cell adhesion of HL-60 cells to recombinant soluble human E-selectin.