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 is reported. Such modifications would 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: (a) SE glycosides can be smoothly transformed into other glycosides via the corresponding glycosyl donors such as 1-chloro sugars and (b) desirable functional groups can be introduced on the amino group by treatment with desired electrophiles such as acyl halides. 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 human leukocyte (HL-60) to recombinant soluble human E-selectin.
