Synthetic studies of heparan derivatives: Glycosyl couplings and post-glycosylative modifications

<p>Heparan sulfate (HS) and closely related heparin are comprised of alternating units of D-glucosamine and either D-glucuronic acid (D-GluA) or L-iduronic acid (L-IdoA), and support variable degrees of sulfation which can interact with a large number of proteins with diverse biological functions. HS oligosaccharides can be constructed from readily accessible D-GlcN and D-GlcA derivatives, but the inclusion of L-IdoA is less straightforward. To address this, our laboratory has developed alternative synthetic strategies for HS-like oligosaccharides to incorporate either D-GlcA or L-IdoA in a synthetically efficient manner by nucleophilic ring opening of 4-epoxypyranosides, which can be made from readily available D-hexoses in few steps. These are derived from 4-deoxypentenosides (4-DPs), unsaturated pyranosides that can be linked with other sugars, enabling us to investigate synthetic strategies involving post-glycosylative modifications. Terminal 4-DPs have been generated at a late stage from β-1,4-linked disaccharides, and also by stereoselective coupling of 4-DP thioglycoside donors with various acceptors. The 4’-enol ether can be modified by stereoselective epoxidation and ring opening by a dithiocarbamate auxiliary, which can be activated by copper(I) salts for carbon nucleophile addition with terminal L-<em>ido</em> configuration. We also explored stereoselective glycosylation of a novel glucosamine donor with a <em>N</em>-diphenylphosphinamido group.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Year

2016

Author dc:creator

• Khatri, Hari Raj

Contributors dc:contributor

• Alexander Wei
• Hilkka I. Kenttamaa
• Chengde Mao
• Christopher Uyeda

• Pure sciences
• 4'-Deoxypentenosyl
• C-furylation
• C2-N-diphenylphosphinic amide
• Heparan sulfate
• L-iduronsyl unit
• Postglycosylative modifications
• Organic Chemistry

Repository record dc:identifier

https://docs.lib.purdue.edu/open_access_dissertations/784

OAI identifier oai:identifier

oai:docs.lib.purdue.edu:open_access_dissertations-1976