Structure–Reactivity Relationships of Conformationally Armed Disaccharide Donors and Their Use in the Synthesis of a Hexasaccharide Related to the Capsular Polysaccharide from Streptococcus pneumoniae Type 37

To
advance the field of glycobiology, efficient synthesis methods
of oligosaccharides and glycoconjugates are a requisite. In glycosylation
reactions using superarmed donors, both selectivity and reactivity
issues must be considered, and we herein investigate these aspects
for differently protected β-linked 2-O-glycosylated
glucosyl donors carrying bulky tert-butyldimethylsilyl
groups to different extents. The acceptors in reactions being secondary
alcohols presents a challenging situation with respect to steric crowding.
Conformational pyranose ring equilibria of the superarmed disaccharide
donors with axial-rich substituents contained skew and boat conformations,
and three-state models were generally assumed. With NIS/TfOH as the
promotor, 2,6-di-tert-butyl-4-methylpyridine as the
base, and a dichloromethane/toluene solvent mixture, ethyl 1-thio-β-d-glucosyl disaccharide donors having 6-O-benzyl
group(s) besides tert-butyldimethylsilyl groups were
efficiently coupled at −40 °C to the hydroxyl group at
position 3 of glucopyranosyl acceptors to form β-(1 →
2),β-(1 → 3)-linked trisaccharides, isolated in excellent
95% yield. The more axial-rich donors in skew and boat conformations
are thus preorganized closer to the assumed transition state in these
glycosylation reactions. The developed methodology was subsequently
applied in the synthesis of a multibranched hexasaccharide related
to the capsular polysaccharide from Streptococcus pneumoniae type 37, which consists of a β-(1 → 3)-linked backbone
and a β-(1 → 2)-linked side chain of d-glucosyl
residues in disaccharide repeating units.