{"id":{"repo_id":"ucl","oai_identifier":"oai:eprints.ucl.ac.uk.OAI2:15938"},"canonical_url":"https://search.dev.ndltd.org/etd/ucl/oai:eprints.ucl.ac.uk.OAI2:15938","repository":{"repo_id":"ucl","name":"University College London","base_url":"https://discovery.ucl.ac.uk/cgi/oai2"},"display":{"title":"Synthesis of functionalised sulfonamides","abstract":"Sulfonamides are important therapeutic agents and have a diverse array of biological functions in biology and medicine. Their means of synthesis has often involved the use of unstable sulfonyl chloride species; however, recent research has established pentafluorophenyl (PFP) sulfonate esters as a useful stable alternative to such species. This thesis describes the use of PFP vinyl sulfonate in a [3+2] cycloaddition with a variety of N-methyl-nitrones, providing access to the corresponding 4C-substituted isoxazolidine in a regio- and diastereoselective manner. Aminolysis of the resultant PFP sulfonate ester then provides functionalised sulfonamides of potential biological utility. In addition, the [3+2] cycloaddition reaction of several vinyl sulfonamides with N-methyl-nitrones is reported. Regiospecificity of the reaction is poor, nevertheless a diverse collection of heterocyclic sulfonamide structures have been isolated. Further attempts to further diversify the isoxazolidine products generated from [3+2] cycloaddition chemistry were carried out. The synthesis of isoxazoles from isoxazolidines was explored, and in the process a novel tertiary amine catalysed 'cycloaddition' has been discovered. The resulting isoxazolidine products were assessed as potential biological probes against various enzymes/diseases, and as a result a collection of products were submitted for biological evaluation against the enzymes dimethylarginine dimethylamino hydrolase (DDAH) and arginine deiminase (ADI). Several compounds displayed \\muM inhibition against DDAH and ADI; and in addition, these currently represent the first known inhibitors of ADI. During the course of our investigation, it was also revealed that a small assortment of our heterocyclic sulfonamides possess good anti-HIV activity at concentrations of 75-100\\muM. Attempts to isolate the cellular target, through modifications to our drug candidates for the purpose of affinity chromatography have also been explored.","abstract_html":"Sulfonamides are important therapeutic agents and have a diverse array of biological functions in biology and medicine. Their means of synthesis has often involved the use of unstable sulfonyl chloride species; however, recent research has established pentafluorophenyl (PFP) sulfonate esters as a useful stable alternative to such species. This thesis describes the use of PFP vinyl sulfonate in a [3+2] cycloaddition with a variety of N-methyl-nitrones, providing access to the corresponding 4C-substituted isoxazolidine in a regio- and diastereoselective manner. Aminolysis of the resultant PFP sulfonate ester then provides functionalised sulfonamides of potential biological utility. In addition, the [3+2] cycloaddition reaction of several vinyl sulfonamides with N-methyl-nitrones is reported. Regiospecificity of the reaction is poor, nevertheless a diverse collection of heterocyclic sulfonamide structures have been isolated. Further attempts to further diversify the isoxazolidine products generated from [3+2] cycloaddition chemistry were carried out. The synthesis of isoxazoles from isoxazolidines was explored, and in the process a novel tertiary amine catalysed 'cycloaddition' has been discovered. The resulting isoxazolidine products were assessed as potential biological probes against various enzymes/diseases, and as a result a collection of products were submitted for biological evaluation against the enzymes dimethylarginine dimethylamino hydrolase (DDAH) and arginine deiminase (ADI). Several compounds displayed \\muM inhibition against DDAH and ADI; and in addition, these currently represent the first known inhibitors of ADI. During the course of our investigation, it was also revealed that a small assortment of our heterocyclic sulfonamides possess good anti-HIV activity at concentrations of 75-100\\muM. Attempts to isolate the cellular target, through modifications to our drug candidates for the purpose of affinity chromatography have also been explored.","abstract_has_math":false,"creators":["Mok, B.L."],"institution":"UCL (University College London)","degree_name":null,"degree_level":"Doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2008,"date_issued":"2008-07","date_published":"2008-07","updated_at":"2026-07-24T05:10:54Z","subjects":["Department of Chemistry"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Mok, B.L."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2008-07"]},{"key":"dc:date.issued","label":"Date","values":["2008-07"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Department of Chemistry"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["UCL (University College London)"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://discovery.ucl.ac.uk/id/eprint/15938/"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Department of Chemistry"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://discovery.ucl.ac.uk/id/eprint/15938/1/U591637.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Sulfonamides are important therapeutic agents and have a diverse array of biological functions in biology and medicine. Their means of synthesis has often involved the use of unstable sulfonyl chloride species; however, recent research has established pentafluorophenyl (PFP) sulfonate esters as a useful stable alternative to such species. This thesis describes the use of PFP vinyl sulfonate in a [3+2] cycloaddition with a variety of N-methyl-nitrones, providing access to the corresponding 4C-substituted isoxazolidine in a regio- and diastereoselective manner. Aminolysis of the resultant PFP sulfonate ester then provides functionalised sulfonamides of potential biological utility. In addition, the [3+2] cycloaddition reaction of several vinyl sulfonamides with N-methyl-nitrones is reported. Regiospecificity of the reaction is poor, nevertheless a diverse collection of heterocyclic sulfonamide structures have been isolated. Further attempts to further diversify the isoxazolidine products generated from [3+2] cycloaddition chemistry were carried out. The synthesis of isoxazoles from isoxazolidines was explored, and in the process a novel tertiary amine catalysed 'cycloaddition' has been discovered. The resulting isoxazolidine products were assessed as potential biological probes against various enzymes/diseases, and as a result a collection of products were submitted for biological evaluation against the enzymes dimethylarginine dimethylamino hydrolase (DDAH) and arginine deiminase (ADI). Several compounds displayed \\muM inhibition against DDAH and ADI; and in addition, these currently represent the first known inhibitors of ADI. During the course of our investigation, it was also revealed that a small assortment of our heterocyclic sulfonamides possess good anti-HIV activity at concentrations of 75-100\\muM. Attempts to isolate the cellular target, through modifications to our drug candidates for the purpose of affinity chromatography have also been explored."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Synthesis of functionalised sulfonamides"]}]}],"canonical_facts":{"dc:creator":["Mok, B.L."],"dc:date":["2008-07"],"dc:date.issued":["2008-07"],"dc:description.abstract":["Sulfonamides are important therapeutic agents and have a diverse array of biological functions in biology and medicine. Their means of synthesis has often involved the use of unstable sulfonyl chloride species; however, recent research has established pentafluorophenyl (PFP) sulfonate esters as a useful stable alternative to such species. This thesis describes the use of PFP vinyl sulfonate in a [3+2] cycloaddition with a variety of N-methyl-nitrones, providing access to the corresponding 4C-substituted isoxazolidine in a regio- and diastereoselective manner. Aminolysis of the resultant PFP sulfonate ester then provides functionalised sulfonamides of potential biological utility. In addition, the [3+2] cycloaddition reaction of several vinyl sulfonamides with N-methyl-nitrones is reported. Regiospecificity of the reaction is poor, nevertheless a diverse collection of heterocyclic sulfonamide structures have been isolated. Further attempts to further diversify the isoxazolidine products generated from [3+2] cycloaddition chemistry were carried out. The synthesis of isoxazoles from isoxazolidines was explored, and in the process a novel tertiary amine catalysed 'cycloaddition' has been discovered. The resulting isoxazolidine products were assessed as potential biological probes against various enzymes/diseases, and as a result a collection of products were submitted for biological evaluation against the enzymes dimethylarginine dimethylamino hydrolase (DDAH) and arginine deiminase (ADI). Several compounds displayed \\muM inhibition against DDAH and ADI; and in addition, these currently represent the first known inhibitors of ADI. During the course of our investigation, it was also revealed that a small assortment of our heterocyclic sulfonamides possess good anti-HIV activity at concentrations of 75-100\\muM. Attempts to isolate the cellular target, through modifications to our drug candidates for the purpose of affinity chromatography have also been explored."],"dc:format":["application/pdf"],"dc:identifier.uri":["https://discovery.ucl.ac.uk/id/eprint/15938/1/U591637.pdf"],"dc:language":["en"],"dc:publisher.department":["Department of Chemistry"],"dc:publisher.institution":["UCL (University College London)"],"dc:relation.isreferencedby":["https://discovery.ucl.ac.uk/id/eprint/15938/"],"dc:subject":["Department of Chemistry"],"dc:title":["Synthesis of functionalised sulfonamides"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["Doctoral"]},"updated_at":"2026-07-24T05:10:54Z"}