{"id":{"repo_id":"east-anglia","oai_identifier":"oai:ueaeprints.uea.ac.uk:48045"},"canonical_url":"https://search.dev.ndltd.org/etd/east-anglia/oai:ueaeprints.uea.ac.uk:48045","repository":{"repo_id":"east-anglia","name":"University of East Anglia","base_url":"https://ueaeprints.uea.ac.uk/cgi/oai2"},"display":{"title":"Towards the Synthesis of the Oxaspirobicyclic Unit of Tetronothiodin","abstract":"The!work!described!in!this!thesis!is!focused!on!the!preparation!of!the!oxaspirobicyclic!tetronic! acid!fragment!2!of!the!CCK%B!receptor!antagonist!tetronothiodin!1.!An!isomer!of!this!compound! has! already! been! synthesized! within! the! Page! group,! however! this! was! found! to! have! the! opposite!stereochemistry!at!the!spiro!centre!to!that!reported!for!the!natural!product.!! ! ! Figure!1:!Structures!of!tetronothiodin!and!the!oxaspirobicyclic!unit.! ! The! thesis! (chapter! I)! first!entails! the!biology!and! chemistry! related! to! tetronothiodin!and! its! cholescystokinin!receptor.!Cholescystokinin!(CCK)!is!a!33%amino!acid!peptide,!which!functions!as! a! digestive! peripheral! hormone! in! the! mammalian! gastrointestinal! tract! and! as! a! neurotransmitter! in! the! central! nervous! system,! where! it! is! more! widely! distributed.! Tetronothiodin!1!is!a!novel!brain%type!CCK!receptor!antagonist,!isolated!from!the!culture!broth! of!Streptomyces!sp.!NR0489.!Various!strategies!of!oxaspirobicyclic!fragment!synthesis!using!the! Diels%Alder! reaction! as! the! key! step! have! been! detailed,! especially! the! work! previously! performed!within!the!Page!group.! ! The! second! part! of! the! thesis! covers! research! work! towards! the! synthesis! of! the! oxaspirobicyclic! unit.! The! synthetic! route! was! proposed! following! the! work! previously! conducted!in!our!laboratories!and!a!solid!knowledge!acquired!about!the!target!molecule.!The! different!investigations!carried!out!within!the!Page!group!have!led!to!a!new!approach,!based!on! a! non%selective! α%hydroxylation! of! a! silyl! enol! ether!moiety,! resulting! in! the! formation! of! a! mixture!of!two!diastereoisomers! in! a!5:3! ratio,! including! the!more!hindered! isomer!with! the! desired! stereochemistry! at! the! pro%spiro! centre! as! the! minor! adduct.! However,! as! the! HO S O O O HO O HO2C H O O O HO EtO O Tetronothiodin Oxaspirobicyclic tetronic acid unit 1 2 ! ! iii! separation! of! the!mixture!was! rather! challenging,!we! decided! to! attempt! different!methods! such!as!the!inversion!of!configuration!of!the!pro%spiro!carbon!atom!bearing!the!hydroxyl!group.! Obtainment! of! the! desired! hydroxyaldehyde! from! a! silyl! enol! ether! is! followed! by! a! Pinnick! reaction!to!give!the!corresponding!carboxylic!acid.! ! The!remaining!synthetic!steps!to!reach!the!oxaspirobicylic!unit!are!rapidly!described.!","abstract_html":"The!work!described!in!this!thesis!is!focused!on!the!preparation!of!the!oxaspirobicyclic!tetronic! acid!fragment!2!of!the!CCK%B!receptor!antagonist!tetronothiodin!1.!An!isomer!of!this!compound! has! already! been! synthesized! within! the! Page! group,! however! this! was! found! to! have! the! opposite!stereochemistry!at!the!spiro!centre!to!that!reported!for!the!natural!product.!! ! ! Figure!1:!Structures!of!tetronothiodin!and!the!oxaspirobicyclic!unit.! ! The! thesis! (chapter! I)! first!entails! the!biology!and! chemistry! related! to! tetronothiodin!and! its! cholescystokinin!receptor.!Cholescystokinin!(CCK)!is!a!33%amino!acid!peptide,!which!functions!as! a! digestive! peripheral! hormone! in! the! mammalian! gastrointestinal! tract! and! as! a! neurotransmitter! in! the! central! nervous! system,! where! it! is! more! widely! distributed.! Tetronothiodin!1!is!a!novel!brain%type!CCK!receptor!antagonist,!isolated!from!the!culture!broth! of!Streptomyces!sp.!NR0489.!Various!strategies!of!oxaspirobicyclic!fragment!synthesis!using!the! Diels%Alder! reaction! as! the! key! step! have! been! detailed,! especially! the! work! previously! performed!within!the!Page!group.! ! The! second! part! of! the! thesis! covers! research! work! towards! the! synthesis! of! the! oxaspirobicyclic! unit.! The! synthetic! route! was! proposed! following! the! work! previously! conducted!in!our!laboratories!and!a!solid!knowledge!acquired!about!the!target!molecule.!The! different!investigations!carried!out!within!the!Page!group!have!led!to!a!new!approach,!based!on! a! non%selective! α%hydroxylation! of! a! silyl! enol! ether!moiety,! resulting! in! the! formation! of! a! mixture!of!two!diastereoisomers! in! a!5:3! ratio,! including! the!more!hindered! isomer!with! the! desired! stereochemistry! at! the! pro%spiro! centre! as! the! minor! adduct.! However,! as! the! HO S O O O HO O HO2C H O O O HO EtO O Tetronothiodin Oxaspirobicyclic tetronic acid unit 1 2 ! ! iii! separation! of! the!mixture!was! rather! challenging,!we! decided! to! attempt! different!methods! such!as!the!inversion!of!configuration!of!the!pro%spiro!carbon!atom!bearing!the!hydroxyl!group.! Obtainment! of! the! desired! hydroxyaldehyde! from! a! silyl! enol! ether! is! followed! by! a! Pinnick! reaction!to!give!the!corresponding!carboxylic!acid.! ! The!remaining!synthetic!steps!to!reach!the!oxaspirobicylic!unit!are!rapidly!described.!","abstract_has_math":false,"creators":["Wang, Wei-Wei"],"institution":"University of East Anglia","degree_name":"phd","degree_level":"doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2012,"date_issued":"2012-10","date_published":"2012-10","updated_at":"2026-07-24T02:11:59Z","subjects":[],"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":["Wang, Wei-Wei"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2012-10"]},{"key":"dc:date.issued","label":"Date","values":["2012-10"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["School of Chemistry"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of East Anglia"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://ueaeprints.uea.ac.uk/id/eprint/48045/"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["phd"]}]},{"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://ueaeprints.uea.ac.uk/id/eprint/48045/1/Wei-Wei%27s_thesis.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The!work!described!in!this!thesis!is!focused!on!the!preparation!of!the!oxaspirobicyclic!tetronic! acid!fragment!2!of!the!CCK%B!receptor!antagonist!tetronothiodin!1.!An!isomer!of!this!compound! has! already! been! synthesized! within! the! Page! group,! however! this! was! found! to! have! the! opposite!stereochemistry!at!the!spiro!centre!to!that!reported!for!the!natural!product.!! ! ! Figure!1:!Structures!of!tetronothiodin!and!the!oxaspirobicyclic!unit.! ! The! thesis! (chapter! I)! first!entails! the!biology!and! chemistry! related! to! tetronothiodin!and! its! cholescystokinin!receptor.!Cholescystokinin!(CCK)!is!a!33%amino!acid!peptide,!which!functions!as! a! digestive! peripheral! hormone! in! the! mammalian! gastrointestinal! tract! and! as! a! neurotransmitter! in! the! central! nervous! system,! where! it! is! more! widely! distributed.! Tetronothiodin!1!is!a!novel!brain%type!CCK!receptor!antagonist,!isolated!from!the!culture!broth! of!Streptomyces!sp.!NR0489.!Various!strategies!of!oxaspirobicyclic!fragment!synthesis!using!the! Diels%Alder! reaction! as! the! key! step! have! been! detailed,! especially! the! work! previously! performed!within!the!Page!group.! ! The! second! part! of! the! thesis! covers! research! work! towards! the! synthesis! of! the! oxaspirobicyclic! unit.! The! synthetic! route! was! proposed! following! the! work! previously! conducted!in!our!laboratories!and!a!solid!knowledge!acquired!about!the!target!molecule.!The! different!investigations!carried!out!within!the!Page!group!have!led!to!a!new!approach,!based!on! a! non%selective! α%hydroxylation! of! a! silyl! enol! ether!moiety,! resulting! in! the! formation! of! a! mixture!of!two!diastereoisomers! in! a!5:3! ratio,! including! the!more!hindered! isomer!with! the! desired! stereochemistry! at! the! pro%spiro! centre! as! the! minor! adduct.! However,! as! the! HO S O O O HO O HO2C H O O O HO EtO O Tetronothiodin Oxaspirobicyclic tetronic acid unit 1 2 ! ! iii! separation! of! the!mixture!was! rather! challenging,!we! decided! to! attempt! different!methods! such!as!the!inversion!of!configuration!of!the!pro%spiro!carbon!atom!bearing!the!hydroxyl!group.! Obtainment! of! the! desired! hydroxyaldehyde! from! a! silyl! enol! ether! is! followed! by! a! Pinnick! reaction!to!give!the!corresponding!carboxylic!acid.! ! The!remaining!synthetic!steps!to!reach!the!oxaspirobicylic!unit!are!rapidly!described.!"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Towards the Synthesis of the Oxaspirobicyclic Unit of Tetronothiodin"]}]}],"canonical_facts":{"dc:creator":["Wang, Wei-Wei"],"dc:date":["2012-10"],"dc:date.issued":["2012-10"],"dc:description.abstract":["The!work!described!in!this!thesis!is!focused!on!the!preparation!of!the!oxaspirobicyclic!tetronic! acid!fragment!2!of!the!CCK%B!receptor!antagonist!tetronothiodin!1.!An!isomer!of!this!compound! has! already! been! synthesized! within! the! Page! group,! however! this! was! found! to! have! the! opposite!stereochemistry!at!the!spiro!centre!to!that!reported!for!the!natural!product.!! ! ! Figure!1:!Structures!of!tetronothiodin!and!the!oxaspirobicyclic!unit.! ! The! thesis! (chapter! I)! first!entails! the!biology!and! chemistry! related! to! tetronothiodin!and! its! cholescystokinin!receptor.!Cholescystokinin!(CCK)!is!a!33%amino!acid!peptide,!which!functions!as! a! digestive! peripheral! hormone! in! the! mammalian! gastrointestinal! tract! and! as! a! neurotransmitter! in! the! central! nervous! system,! where! it! is! more! widely! distributed.! Tetronothiodin!1!is!a!novel!brain%type!CCK!receptor!antagonist,!isolated!from!the!culture!broth! of!Streptomyces!sp.!NR0489.!Various!strategies!of!oxaspirobicyclic!fragment!synthesis!using!the! Diels%Alder! reaction! as! the! key! step! have! been! detailed,! especially! the! work! previously! performed!within!the!Page!group.! ! The! second! part! of! the! thesis! covers! research! work! towards! the! synthesis! of! the! oxaspirobicyclic! unit.! The! synthetic! route! was! proposed! following! the! work! previously! conducted!in!our!laboratories!and!a!solid!knowledge!acquired!about!the!target!molecule.!The! different!investigations!carried!out!within!the!Page!group!have!led!to!a!new!approach,!based!on! a! non%selective! α%hydroxylation! of! a! silyl! enol! ether!moiety,! resulting! in! the! formation! of! a! mixture!of!two!diastereoisomers! in! a!5:3! ratio,! including! the!more!hindered! isomer!with! the! desired! stereochemistry! at! the! pro%spiro! centre! as! the! minor! adduct.! However,! as! the! HO S O O O HO O HO2C H O O O HO EtO O Tetronothiodin Oxaspirobicyclic tetronic acid unit 1 2 ! ! iii! separation! of! the!mixture!was! rather! challenging,!we! decided! to! attempt! different!methods! such!as!the!inversion!of!configuration!of!the!pro%spiro!carbon!atom!bearing!the!hydroxyl!group.! Obtainment! of! the! desired! hydroxyaldehyde! from! a! silyl! enol! ether! is! followed! by! a! Pinnick! reaction!to!give!the!corresponding!carboxylic!acid.! ! The!remaining!synthetic!steps!to!reach!the!oxaspirobicylic!unit!are!rapidly!described.!"],"dc:format":["application/pdf"],"dc:identifier.uri":["https://ueaeprints.uea.ac.uk/id/eprint/48045/1/Wei-Wei%27s_thesis.pdf"],"dc:language":["en"],"dc:publisher.department":["School of Chemistry"],"dc:publisher.institution":["University of East Anglia"],"dc:relation.isreferencedby":["https://ueaeprints.uea.ac.uk/id/eprint/48045/"],"dc:title":["Towards the Synthesis of the Oxaspirobicyclic Unit of Tetronothiodin"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["doctoral"],"dc:type.qualificationname":["phd"]},"updated_at":"2026-07-24T02:11:59Z"}