{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/70285"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/70285","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Halo Enol Lactones as Enzyme-Activated Irreversible Inhibitors of Alpha-Chymotrypsin: I. The Effect of Lactone Substitution Pattern. Ii. Alpha - Amino-Functionalized Lactones","abstract":"Halo enol lactones with a phenyl group situated (beta) or (gamma) to the lactone carbonyl group were prepared to compare their effectiveness as enzyme-activated irreversible (suicide) inhibitors for (alpha)-chymotrypsin with the activities of the corresponding (alpha)-substituted lactones. The 4-phenyl-5(E)-(iodomethylidene) tetrahydro-2-furanone, the 4-phenyl-5(E)-(iodomethylidene)dihydro-2-furanone, the 4-phenyl-6(E)-(iodomethylidene)tetrahydro-2-pyranone and the 5-phenyl-6(E)-(iodomethylidene)tetrahydro-2-pyranone were prepared using a halolactonization reaction to convert the appropriate phenyl-substituted acetylenic acid into the corresponding lactone. The 4-phenyl-tetrahydrofuranone and the 5-phenyl-tetrahydropyranone only proved to be competitive inhibitors, and the 4-phenyl-dihydrofuranone appeared to be neither an irreversible inhibitor nor a competitive inhibitor. However, the 4-phenyl-tetrahydropyranone temporarily inactivated (alpha)-chymotrypsin presumably by the formation of a stable acyl-enzyme complex as suggested by experimental data.","abstract_html":"Halo enol lactones with a phenyl group situated (beta) or (gamma) to the lactone carbonyl group were prepared to compare their effectiveness as enzyme-activated irreversible (suicide) inhibitors for (alpha)-chymotrypsin with the activities of the corresponding (alpha)-substituted lactones. The 4-phenyl-5(E)-(iodomethylidene) tetrahydro-2-furanone, the 4-phenyl-5(E)-(iodomethylidene)dihydro-2-furanone, the 4-phenyl-6(E)-(iodomethylidene)tetrahydro-2-pyranone and the 5-phenyl-6(E)-(iodomethylidene)tetrahydro-2-pyranone were prepared using a halolactonization reaction to convert the appropriate phenyl-substituted acetylenic acid into the corresponding lactone. The 4-phenyl-tetrahydrofuranone and the 5-phenyl-tetrahydropyranone only proved to be competitive inhibitors, and the 4-phenyl-dihydrofuranone appeared to be neither an irreversible inhibitor nor a competitive inhibitor. However, the 4-phenyl-tetrahydropyranone temporarily inactivated (alpha)-chymotrypsin presumably by the formation of a stable acyl-enzyme complex as suggested by experimental data.","abstract_has_math":false,"creators":["Sofia, Michael Joseph"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2014,"date_issued":"2014-12-15T23:18:23Z","date_published":"2014-12-15T23:18:23Z","updated_at":"2026-07-22T22:26:02Z","subjects":["Chemistry, Organic"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["(UMI)AAI8502303"],"render_values":[{"text":"(UMI)AAI8502303","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2142/70285","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Sofia, Michael Joseph"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2014-12-15T23:18:23Z","10000-01-01","1984"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"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":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Chemistry, Organic"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/70285","(UMI)AAI8502303"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Halo enol lactones with a phenyl group situated (beta) or (gamma) to the lactone carbonyl group were prepared to compare their effectiveness as enzyme-activated irreversible (suicide) inhibitors for (alpha)-chymotrypsin with the activities of the corresponding (alpha)-substituted lactones. The 4-phenyl-5(E)-(iodomethylidene) tetrahydro-2-furanone, the 4-phenyl-5(E)-(iodomethylidene)dihydro-2-furanone, the 4-phenyl-6(E)-(iodomethylidene)tetrahydro-2-pyranone and the 5-phenyl-6(E)-(iodomethylidene)tetrahydro-2-pyranone were prepared using a halolactonization reaction to convert the appropriate phenyl-substituted acetylenic acid into the corresponding lactone. The 4-phenyl-tetrahydrofuranone and the 5-phenyl-tetrahydropyranone only proved to be competitive inhibitors, and the 4-phenyl-dihydrofuranone appeared to be neither an irreversible inhibitor nor a competitive inhibitor. However, the 4-phenyl-tetrahydropyranone temporarily inactivated (alpha)-chymotrypsin presumably by the formation of a stable acyl-enzyme complex as suggested by experimental data.","Also, (alpha)-amino-functionalized halo enol lactones were prepared by halolactonization of their corresponding acetylenic amino acids and investigated as suicide inhibitors of (alpha)-chymotrypsin. The 3-benzamido-5(E)-(iodomethylidene)tetrahydro-2-furanone, the 3-benzamido-3-benzyl-5(E)-(1-bromoethylidene)tetrahydro-2-furanone, the 3-acetamido-3-benzyl-5(E)-(bromomethylidene)tetrahydro-2-furanone and the 3-amino-3-benzyl-5(E)-(bromomethylidene)tetrahydro-2-furanone were shown to be only competitive inhibitors of (alpha)-chymotrypsin. A 3-benzamido-3-phenyl-5(E)-(bromomethylidene)tetrahydro-2-furanone was found to be an irreversible, but inefficient, suicide inhibitor of (alpha)-chymotrypsin.","3-Acetamido- and 3-benzamido-4-phenyl-6(E)-(iodomethylidene)tetrahydro-2-pyranones ((3R*,4R*) and (3R*,4S*)) also proved not to be suicide inhibitors of (alpha)-chymotrypsin. Experimental evidence indicates that these lactones inactivate (alpha)-chymotrypsin by a pseudosuicide mechanism or by the intermediacy of a spontaneously generated reactive species.","Made available in DSpace on 2014-12-15T23:18:23Z (GMT). No. of bitstreams: 1 8502303.pdf: 6682539 bytes, checksum: 0cdb0e91e3c1667ed665f8073b7198f9 (MD5) Previous issue date: 1984","Embargo set by: Seth Robbins for item 70451 Lift date: Forever Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","U of I Only","241 p.","Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1984."]},{"key":"dc:title","label":"Title","values":["Halo Enol Lactones as Enzyme-Activated Irreversible Inhibitors of Alpha-Chymotrypsin: I. The Effect of Lactone Substitution Pattern. Ii. Alpha - Amino-Functionalized Lactones"]}]}],"canonical_facts":{"dc:creator":["Sofia, Michael Joseph"],"dc:date":["2014-12-15T23:18:23Z","10000-01-01","1984"],"dc:description":["Halo enol lactones with a phenyl group situated (beta) or (gamma) to the lactone carbonyl group were prepared to compare their effectiveness as enzyme-activated irreversible (suicide) inhibitors for (alpha)-chymotrypsin with the activities of the corresponding (alpha)-substituted lactones. The 4-phenyl-5(E)-(iodomethylidene) tetrahydro-2-furanone, the 4-phenyl-5(E)-(iodomethylidene)dihydro-2-furanone, the 4-phenyl-6(E)-(iodomethylidene)tetrahydro-2-pyranone and the 5-phenyl-6(E)-(iodomethylidene)tetrahydro-2-pyranone were prepared using a halolactonization reaction to convert the appropriate phenyl-substituted acetylenic acid into the corresponding lactone. The 4-phenyl-tetrahydrofuranone and the 5-phenyl-tetrahydropyranone only proved to be competitive inhibitors, and the 4-phenyl-dihydrofuranone appeared to be neither an irreversible inhibitor nor a competitive inhibitor. However, the 4-phenyl-tetrahydropyranone temporarily inactivated (alpha)-chymotrypsin presumably by the formation of a stable acyl-enzyme complex as suggested by experimental data.","Also, (alpha)-amino-functionalized halo enol lactones were prepared by halolactonization of their corresponding acetylenic amino acids and investigated as suicide inhibitors of (alpha)-chymotrypsin. The 3-benzamido-5(E)-(iodomethylidene)tetrahydro-2-furanone, the 3-benzamido-3-benzyl-5(E)-(1-bromoethylidene)tetrahydro-2-furanone, the 3-acetamido-3-benzyl-5(E)-(bromomethylidene)tetrahydro-2-furanone and the 3-amino-3-benzyl-5(E)-(bromomethylidene)tetrahydro-2-furanone were shown to be only competitive inhibitors of (alpha)-chymotrypsin. A 3-benzamido-3-phenyl-5(E)-(bromomethylidene)tetrahydro-2-furanone was found to be an irreversible, but inefficient, suicide inhibitor of (alpha)-chymotrypsin.","3-Acetamido- and 3-benzamido-4-phenyl-6(E)-(iodomethylidene)tetrahydro-2-pyranones ((3R*,4R*) and (3R*,4S*)) also proved not to be suicide inhibitors of (alpha)-chymotrypsin. Experimental evidence indicates that these lactones inactivate (alpha)-chymotrypsin by a pseudosuicide mechanism or by the intermediacy of a spontaneously generated reactive species.","Made available in DSpace on 2014-12-15T23:18:23Z (GMT). No. of bitstreams: 1 8502303.pdf: 6682539 bytes, checksum: 0cdb0e91e3c1667ed665f8073b7198f9 (MD5) Previous issue date: 1984","Embargo set by: Seth Robbins for item 70451 Lift date: Forever Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","U of I Only","241 p.","Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1984."],"dc:identifier":["http://hdl.handle.net/2142/70285","(UMI)AAI8502303"],"dc:subject":["Chemistry, Organic"],"dc:title":["Halo Enol Lactones as Enzyme-Activated Irreversible Inhibitors of Alpha-Chymotrypsin: I. The Effect of Lactone Substitution Pattern. Ii. Alpha - Amino-Functionalized Lactones"],"dc:type":["text"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:26:02Z"}