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 beta-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-beta-d-glucosyl disaccharide donors having 6-O-benzyl group(s) besides tert-butyldimethylsilyl groups were efficiently coupled at -40 degrees C to the hydroxyl group at position 3 of glucopyranosyl acceptors to form beta-(1 -> 2),beta-(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 beta-(1 -> 3)-linked backbone and a beta-(1 -> 2)-linked side chain of D-glucosyl residues in disaccharide repeating units.

Subject headings

NATURVETENSKAP  -- Kemi -- Organisk kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences -- Organic Chemistry (hsv//eng)

Keyword

organisk kemi

Organic Chemistry

Publication and Content Type

ref (subject category)

art (subject category)