Polymer-supported solution synthesis of oligosaccharides

• US 5,278,303 A
• Filed: 06/12/1992
• Issued: 01/11/1994
• Est. Priority Date: 06/12/1992
• Status: Expired due to Fees

• Current Assignee: University of Toronto Innovations Foundation
• Original Assignee: University of Toronto Innovations Foundation
• Inventors: Whitfield, Dennis M., Krepinsky, Jiri J., Douglas, Stephen P.
• Primary Examiner(s): Lilling, Herbert J.
• Application Number:
  US07/898,030
• Time in Patent Office: 578 Days
• Field of Search: 527/311, 527/300, 527/312, 536/49, 536/50, 536/55.3, 536/116, 536/120, 536/126, 530/124
• US Class Current: 536/55.3
• CPC Class Codes: C07H 15/04 attached to an oxygen atom of the saccharide radical
• CPC Class Codes: C07H 3/06 Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages

Abstract

This invention relates to the preparation of oligosaccharides, using polymer supported methodology. By this method, which offers anomeric control, oligosaccharides are produced very rapidly in comparison with known methodologies. Thus, there is disclosed a process for the preparation of oligosaccharides which comprises

a) forming a synthon of a saccharide and a monomethylether of polyethylene glycol or a derivative thereof, the synthon having a linkage between the oligosaccharide and the monomethylether of polyethylene glycol or a derivative thereof, which linkage can be severed under conditions that do not damage glycosidic or other bonds in a desired end product;

b) subjecting the synthon to repeated additions of a suitable glycosylating agent to form a desired oligosaccharide-polyethylene glycol linked product;

c) isolating the linked product as a solid;

d) purifying this solid; and

e) releasing the oligosaccharide from the polyethylene glycol.

Claims

1. A process for the preparation of oligosaccharides which comprises:

a) reacting a first reactant saccharide having at least one monosaccharide unit with a second reactant which is a polyethylene glycol monomethyl ether, the two reactants being linked through an ester linkage of dicarboxylic acid bound to a carbohydrate carboxyl;

b) subjecting the saccharide-polyethylene glycol monomethyl ether reaction product to a glycosylation reaction through a plurality of additions of a glycosylation agent having an activated anomeric center, while monitoring the reaction for completion;

c) isolating the polyethylene glycol-oligosaccharide as a solid;

d) purifying the solid; and

e) releasing the oligosaccharide from the polyethylene glycol.

2. The method of claim 1 wherein said dicarboxylic acid is succinic acid.

3. The method of claim 1 wherein said isolating step comprises precipitation in the presence of an anhydrous solvent.

4. The method of claim 3 wherein said solvent is anhydrous ether.

5. The method of claim 1 wherein said purification step comprises recrystallization.

6. The method of claim 1 wherein the monitoring step employs magnetic resonance spectroscopy.

7. The method of claim 1 wherein said releasing step comprises hydrolysis.

8. The method of claim 1 wherein the polyethylene glycol has a molecular weight of about 5000.

9. A process as claimed in claim 1 wherein the dicarboxylate group from succinic acid is attached to the polyethylene glycol monomethylether and to a hydroxy group of the oligosaccharide.