Efficient Synthesis of High-Mannose-Type Oligosaccharide as Versatile Tools to Study N-Glycan Biosynthesis Pathway

PS1 Poster session 1 Odd numbers
Location (hall): 
Start/end time: 
Monday, July 1, 2019 - 15:45 to 17:15

Kanae Sano1, Tomomichi Takagaki1, Ayumi Kuroiwa1, Nozomi Ishii1, Ichiro Matsuo1

1Gunma university, Kiryu, Japan

Asparagine (N-) linked oligosaccharides play a critical role in numerous biological events including protein folding and quality control in the endoplasmic reticulum(1). Chemical synthetic access to N-glycans provides access to valuable tools to probe their biological functions. Unfortunately, the chemical synthesis of oligosaccharide is not only labor-intensive but also time-consuming. To overcome these limitations, we envisaged the following strategy; 1) convergent and regioselective construction of N-glycan skelton, 2) employment of a common precursor for the construction of oligosaccharide blocks, 3) stereoselective glycosylation assisted by neighboring group participation. To avoid direct construction of the more challenging β-mannoside bond, we opted to initially create β-galactosides followed by simultaneous double inversion reaction at the C-2 and C-4 hydroxy group.

Following above outlined strategy, we successfully completed the synthesis of high mannose-type sugar chains (Man5GlcNAc2 and Man9GlcNAc2).

Synthetic strategy of high mannose-type sugar chains

  1. A. Helenius and M. Aebi, Roles of N-linked glycans in the endoplasmic reticulum, Annu. Rev. biochem. 2004, 73, 1019-1049.
  2. I. Matsuo, M. Isomura and K. Ajisaka, Synthesis of an asparagine-linked core pentasaccharide by means of simultaneous inversion reactions, J. Carbohydr. Chem. 1999, 18, 841-850.
  3. N. Ishii, K. Sano and I. Matsuo, Fluorogenic probe for measuring high-mannose type glycan-specific endo-β-N-acetylglucosaminidase H activity, Bioorg. Med. Chem. Lett. 2019, 29, 1643-1646.