Oligosaccharides on cell surface play important roles in many biological processes. Most biologically active oligosaccharides are rare, and are difficult to be purified. Additionally, their structural diversity based upon stereo- and regio-isomers makes it difficult to not only determine their structures, but also to accomplish its chemical synthesis in comparison with those of oligopeptides and oligonucleotides. We have investigated the one-pot glycosylation based on the chemoselective activation of glycosyl donors attached with different leaving groups with appropriate activators. Herein we report the high-speed synthesis of biologically active oligosaccharides (dimeric Lewis X and sialo-containing glycosyl amino acids) by one-pot glycosylation. In the first topic, we descried the synthesis of a protected dimeric Lewis X epitope by sequential one-pot glycosylation and an application to the automated synthesis of a protected dimeric Lewis X library. We designed sequential one-pot four-step glycosylations to provide octasaccharide 12 from five different building blocks 2 and 4-7. One-pot glycosylation using 2-5 provided the glycosyl fluoride 3 in good yield. The following one-pot glycosylation involving glycosylation of 2 with the glycosyl fluoride 3 and coupling with additional two building blocks 4 and 5 afforded a protected octasaccharide 12 in excellent yield. The synthesis of 12 member hepta-to di-saccharides 13 and 14 was accomplished by the one-pot glycosylation utilizing an solution-phase automated synthesizer. In the next topic, we report one-pot glycosylation involving sialylation to provide sialo-containing glycosyl amino acids 19 and 20. We first examined glycosidation of thiosialoside varying the protecting group at the C5 amino group. N-Troc thiosialoside 21 was found to be effective for sialylation. Using the sialyl donor 21, linear and branched type one-pot glycosylations were accomplished to provide linear and branched trisaccharides 27 and 31 in excellent yields with good stereoselectivity at the anomeric position.
