Two-step functionalization of oligosaccharides using glycosyl iodide and trimethylene oxide and its applications to multivalent glycoconjugates

Hsiao Wu Hsieh, Ryan A. Davis, Jessica A. Hoch, Jacquelyn Gervay-Hague

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Oligosaccharide conjugates, such as glycoproteins and glycolipids, are potential chemotherapeutics and also serve as useful tools for understanding the biological roles of carbohydrates. With many modern isolation and synthetic technologies providing access to a wide variety of free sugars, there is increasing need for general methodologies for carbohydrate functionalization. Herein, we report a two-step methodology for the conjugation of per-O-acetylated oligosaccharides to functionalized linkers that can be used for various displays. Oligosaccharides obtained from both synthetic and commercial sources were converted to glycosyl iodides and activated with I2 to form reactive donors that were subsequently trapped with trimethylene oxide to form iodopropyl conjugates in a single step. The terminal iodide served as a chemical handle for further modification. Conversion into the corresponding azide followed by copper-catalyzed azide-alkyne cycloaddition afforded multivalent glycoconjugates of Gb3 for further investigation as anti-cancer therapeutics. A two-step methodology for the conjugation of per-O-acetylated oligosaccharides to functionalized linkers, which can be used for various displays, is described. Oligosaccharides were converted to glycosyl iodides and activated with I 2, forming reactive donors, which were subsequently trapped with trimethylene oxide (TMO), forming iodopropyl conjugates. Conversion into the corresponding azide followed by copper-catalyzed azide-alkyne cycloaddition afforded multivalent glycoconjugates of Gb3 for further investigation as anti-cancer therapeutics (see scheme).

Original languageEnglish (US)
Pages (from-to)6444-6454
Number of pages11
JournalChemistry - A European Journal
Volume20
Issue number21
DOIs
StatePublished - May 19 2014

Keywords

  • carbohydrates
  • functionalization
  • glycosyl iodides
  • glycosylation
  • multivalent glycoconjugates

ASJC Scopus subject areas

  • Chemistry(all)

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