Novel methods to expedite oligosaccharide synthesis and their application towards the preparation of mucin type o-glycans

• Main Author: Jones, Rachel A.
• Published: University of Bristol 2013
• Subjects: 572
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.633253

The synthesis of oligosaccharides is known to be a lengthy and time-consuming endeavour. This thesis describes novel methods to expedite the synthesis of carbohydrates and in particular the work centres on mucin O-glycans. The core 3 and core 4 mucin type structures that are found in human mucosal tissue of the digestive tract are specifically targeted. One-pot synthetic strategies were developed. The work illustrates that it is possible to prepare orthogonally protected monosaccharide building blocks from unprotected, commercially available starting materials in high yield within 24 hours. The series of building blocks synthesised using this methodology were subsequently used to prepare a series of protected O-linked di- and trisaccharides. A major obstacle in the synthesis of oligosaccharides is the need for purification via column chromatography following each reaction step. Ionic liquids are a class of compounds that have attracted growing attention over recent years as they can be used as soluble supports (i.e. purification labels) thus allowing chromatography-free purification. The use of ionic liquids has been explored as a means of preparing ~-1 ,3-glycans linear and branched oligosaccharides. In particular, work was canied out to develop new, multifunctional and orthogonal ionic liquid-based linkers for attachment to a monosaccharide unit, such that following oligosaccharide assembly; the product can be cleaved from the soluble suppOli to reveal an amine group that will enable the newly formed oligosaccharide to be attached to glycoarrays.