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

9 Citations (Scopus)

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

Fingerprint

Oligosaccharides
Glycoconjugates
Iodides
Azides
Oxides
Alkynes
Cycloaddition
Carbohydrates
Copper
Display devices
Glycoproteins
Glycolipids
Sugars
oxetane

Keywords

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

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Two-step functionalization of oligosaccharides using glycosyl iodide and trimethylene oxide and its applications to multivalent glycoconjugates. / Hsieh, Hsiao Wu; Davis, Ryan A.; Hoch, Jessica A.; Gervay-Hague, Jacquelyn.

In: Chemistry - A European Journal, Vol. 20, No. 21, 19.05.2014, p. 6444-6454.

Research output: Contribution to journalArticle

@article{8f79cf1cb5234b4db3e63ec63898dc29,
title = "Two-step functionalization of oligosaccharides using glycosyl iodide and trimethylene oxide and its applications to multivalent glycoconjugates",
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).",
keywords = "carbohydrates, functionalization, glycosyl iodides, glycosylation, multivalent glycoconjugates",
author = "Hsieh, {Hsiao Wu} and Davis, {Ryan A.} and Hoch, {Jessica A.} and Jacquelyn Gervay-Hague",
year = "2014",
month = "5",
day = "19",
doi = "10.1002/chem.201400024",
language = "English (US)",
volume = "20",
pages = "6444--6454",
journal = "Chemistry - A European Journal",
issn = "0947-6539",
publisher = "Wiley-VCH Verlag",
number = "21",

}

TY - JOUR

T1 - Two-step functionalization of oligosaccharides using glycosyl iodide and trimethylene oxide and its applications to multivalent glycoconjugates

AU - Hsieh, Hsiao Wu

AU - Davis, Ryan A.

AU - Hoch, Jessica A.

AU - Gervay-Hague, Jacquelyn

PY - 2014/5/19

Y1 - 2014/5/19

N2 - 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).

AB - 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).

KW - carbohydrates

KW - functionalization

KW - glycosyl iodides

KW - glycosylation

KW - multivalent glycoconjugates

UR - http://www.scopus.com/inward/record.url?scp=84900804059&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84900804059&partnerID=8YFLogxK

U2 - 10.1002/chem.201400024

DO - 10.1002/chem.201400024

M3 - Article

AN - SCOPUS:84900804059

VL - 20

SP - 6444

EP - 6454

JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

SN - 0947-6539

IS - 21

ER -