An efficient approach towards the convergent synthesis of "fully-carbohydrate" mannodendrimers

Leon V. Backinowsky*, Polina I. Abronina, Alexander S. Shashkov, Alexey A. Grachev, Nikolay K. Kochetkov, Sergey A. Nepogodiev, J. Fraser Stoddart

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Glycosylation of sugar trityl ethers with sugar 1,2-O-(1-cyano)ethylidene derivatives (the trityl-cyanoethylidene condensation) has been applied to the synthesis of highly branched (dendritic) mannooligosaccharides incorporating a Manα1 → 3(Manα1 → 6)Man structural motif. The convergent synthetic strategy used to assemble these oligosaccharides was based on the use of glycosyl acceptors and/or a glycosyl donor already bearing this structural motif. The former were represented by mono- and ditrityl ethers of MancαOMe, Manα1 → 3ManαOMe, and Manα1 → 3(Manα1 → 6)ManαX, where X = OMe or SEt. The pivotal glycosyl donor was the peracetylated 1,2-O-(1-cyano)ethylidene-3,6-di-O-(α-D-mannopyranosyl)-β -D-mannopyranose (1), prepared by orthogonal Helferich glycosylation of the known 1,2-O-(1-cyano)ethylidene-β-D-mannopyranose with tetra-O-acetyl-α-D-mannopyranosyl bromide followed by O-acetylation. Glycosylation of acetates of methyl 6-O-trityl-α-D-mannopyranoside and methyl 3,6-di-Otrityl-α-D-mannopyranoside with one equivalent of the donor 1 gave rise to the isomeric tetrasaccharide derivatives, Manα1 → 3(Manα1 → 6)Manα1 → 6ManαOMe and Manα1 → 3(Manα1 → 6)Manα1 → 3ManαOMe, respectively. The latter derivative was further mannosylated at the remaining 6-O-trityl acceptor site to give the protected pentasaccharide Manα1 → 3(Manα1 → 3(Manα1 → 6)Manα1 → 3(Manα1 → 6)ManαOMe. The isomeric pentasaccharide, Manα1 → 3(Manα1 → 6)Manα1 → 6(Manα1 → 3)ManαOMe, was prepared by reaction of 1 with the 6-O-trityl derivative of (Manα1 → 3)ManαOMe. In a similar fashion, 6′- and 6″-O-trityl derivatives of the branched trisaccharide Manα1 → 3(Manα1 → 6)ManαOMe served as precursors for two isomeric mannohexaosides. The 3,6-di-O-trityl ether of ManαOMe and the 6′,6″-di-O-trityl ether of Manα1 → 3(Manα1 → 6)ManαX (X= OMe or SEt) were efficiently bis-glycosylated with the donor 1 to give the corresponding protected mannoheptaoside and mannononaoside. The yields of these glycosylations with the donor 1 ranged from 50 to 66%. Final deprotection of all the oligosaccharides was straightforward and afforded the target products in high yields. Both the acylated and deprotected products were characterized, and the intersaccharide connectivities were elucidated by extensive one- and two-dimensional NMR spectroscopy. The described blockwise convergent approach allows assembly of a variety of 3,6-branched mannooligosaccharides.

Original languageEnglish (US)
Pages (from-to)4412-4423
Number of pages12
JournalChemistry - A European Journal
Volume8
Issue number19
DOIs
StatePublished - Oct 4 2002

Keywords

  • Carbohydrates
  • Glycosylation
  • NMR spectroscopy
  • Oligosaccharides
  • Synthetic methods

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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