Toward the automated synthesis of carbohydrates and glycosaminoglycans

Glycosaminoglycans are crucial components of the extracellular matrix and cell surface and access to define sequences is required to fully appreciate their role in biology. As is the case with most complex polysaccharides, the chemical synthesis of glycosaminoglycan structures is challenging. This thesis describes efforts towards the construction of oligosaccharides with the ultimate goal of the automated synthesis of glycosaminoglycans. The use of glycosyl phosphates of glucosamine and glucuronic acid as competent glycosylating agents is illustrated. Further expansion of the glycosyl phosphates methodology to the construction of C-aryl and C-alkyl glycosides and resulted in the synthesis of the natural product 8,1 0-di-O-methylbergenin. The automated solid-phase synthesis of two complex oligosaccharides is described. The complex-type high mannose trisaccharide and the proteoglycan linkage region tetrasaccharide were synthesized in a fully automated fashion. The efforts towards the synthesis of two glycosaminoglycans - hyaluronic acid and chondroitin sulfate - are discussed. The work focuses on the discovery of a glycosylating agent suitable for the automated solid-phase synthesis. The synthesis of glucuronic acid from glucose is described using an oxidation procedure not previously explored in oligosaccharide construction.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemistry.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2003

Author dc:creator

• Palmacci, Emma Rose, 1976-

Advisor dc:contributor.advisor

• Peter H. Seeberger.

• Chemistry.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/29643

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/29643