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-ido configuration. We also explored stereoselective glycosylation of a novel glucosamine donor with a N-diphenylphosphinamido group.
","abstract_html":"<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>","abstract_has_math":false,"creators":["Khatri, Hari Raj"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":["Alexander Wei","Hilkka I. Kenttamaa","Chengde Mao","Christopher Uyeda"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2016,"date_issued":"2016-08-01T07:00:00Z","date_published":"2016-08-01T07:00:00Z","updated_at":"2026-07-24T03:53:55Z","subjects":["Pure sciences","4'-Deoxypentenosyl","C-furylation","C2-N-diphenylphosphinic amide","Heparan sulfate","L-iduronsyl unit","Postglycosylative modifications","Organic Chemistry"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://docs.lib.purdue.edu/open_access_dissertations/784","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Alexander Wei","Hilkka I. Kenttamaa","Chengde Mao","Christopher Uyeda"]},{"key":"dc:creator","label":"Author","values":["Khatri, Hari Raj"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Pure sciences","4'-Deoxypentenosyl","C-furylation","C2-N-diphenylphosphinic amide","Heparan sulfate","L-iduronsyl unit","Postglycosylative modifications","Organic Chemistry"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://docs.lib.purdue.edu/open_access_dissertations/784"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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-ido configuration. We also explored stereoselective glycosylation of a novel glucosamine donor with a N-diphenylphosphinamido group.
"]},{"key":"dc:title","label":"Title","values":["Synthetic studies of heparan derivatives: Glycosyl couplings and post-glycosylative modifications"]}]}],"canonical_facts":{"dc:contributor":["Alexander Wei","Hilkka I. Kenttamaa","Chengde Mao","Christopher Uyeda"],"dc:creator":["Khatri, Hari Raj"],"dc:description.abstract":["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-ido configuration. We also explored stereoselective glycosylation of a novel glucosamine donor with a N-diphenylphosphinamido group.
"],"dc:identifier":["https://docs.lib.purdue.edu/open_access_dissertations/784"],"dc:subject":["Pure sciences","4'-Deoxypentenosyl","C-furylation","C2-N-diphenylphosphinic amide","Heparan sulfate","L-iduronsyl unit","Postglycosylative modifications","Organic Chemistry"],"dc:title":["Synthetic studies of heparan derivatives: Glycosyl couplings and post-glycosylative modifications"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T03:53:55Z"}