{"id":{"repo_id":"soton","oai_identifier":"oai:eprints.soton.ac.uk:193063"},"canonical_url":"https://search.dev.ndltd.org/etd/soton/oai:eprints.soton.ac.uk:193063","repository":{"repo_id":"soton","name":"University of Southampton","base_url":"https://eprints.soton.ac.uk/cgi/oai2"},"display":{"title":"Synthesis of gemcitabine and it's tetrafluorinated analogues","abstract":"A novel synthesis of the 2-deoxy-2,2-difluorocytidine nucleoside analogue gemcitabine has been achieved. Starting from the known 3,5-O-dibenzoyl-2- deoxy-2,2-difluororibose, the nucleobase moiety is constructed in a linear fashion, using amino- or urea glycosylation methodology. This methodology has also been employed to synthesise nucleosides containing a tetrafluorinated ribose sugar and has been compared to conventional convergent nucleobase introduction methods. In this respect, a high-yielding Mitsunobu-based protocol has also been developed. Both purine and pyrimidine analogues have been synthesised. The aminoglycosylation methodology has been investigated with a range of amines. The methodology proves high-yielding for primary amines and lesshindered secondary amines. In contrast to expectations, their stability in acidic media was not very high. Anomerisation and ring isomerisation studies have been conducted","abstract_html":"A novel synthesis of the 2-deoxy-2,2-difluorocytidine nucleoside analogue gemcitabine has been achieved. Starting from the known 3,5-O-dibenzoyl-2- deoxy-2,2-difluororibose, the nucleobase moiety is constructed in a linear fashion, using amino- or urea glycosylation methodology. This methodology has also been employed to synthesise nucleosides containing a tetrafluorinated ribose sugar and has been compared to conventional convergent nucleobase introduction methods. In this respect, a high-yielding Mitsunobu-based protocol has also been developed. Both purine and pyrimidine analogues have been synthesised. The aminoglycosylation methodology has been investigated with a range of amines. The methodology proves high-yielding for primary amines and lesshindered secondary amines. In contrast to expectations, their stability in acidic media was not very high. Anomerisation and ring isomerisation studies have been conducted","abstract_has_math":false,"creators":["Brown, Kylie J."],"institution":"University of Southampton","degree_name":"Ph.D.","degree_level":"doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Linclau, Bruno"],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-04","date_published":"2011-04","updated_at":"2026-07-24T04:36:28Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Linclau, Bruno"]},{"key":"dc:creator","label":"Author","values":["Brown, Kylie J."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2011-04-26"]},{"key":"dc:date.issued","label":"Date","values":["2011-04"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Chemistry (pre 2011 reorg)","Chemistry"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Southampton"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://eprints.soton.ac.uk/193063/"]},{"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":["Ph.D."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://eprints.soton.ac.uk/193063/1/Kylie_Brown_PhD_Thesis.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["A novel synthesis of the 2-deoxy-2,2-difluorocytidine nucleoside analogue gemcitabine has been achieved. Starting from the known 3,5-O-dibenzoyl-2- deoxy-2,2-difluororibose, the nucleobase moiety is constructed in a linear fashion, using amino- or urea glycosylation methodology. This methodology has also been employed to synthesise nucleosides containing a tetrafluorinated ribose sugar and has been compared to conventional convergent nucleobase introduction methods. In this respect, a high-yielding Mitsunobu-based protocol has also been developed. Both purine and pyrimidine analogues have been synthesised. The aminoglycosylation methodology has been investigated with a range of amines. The methodology proves high-yielding for primary amines and lesshindered secondary amines. In contrast to expectations, their stability in acidic media was not very high. Anomerisation and ring isomerisation studies have been conducted"]},{"key":"dc:format","label":"Dc Format","values":["text"]},{"key":"dc:title","label":"Title","values":["Synthesis of gemcitabine and it's tetrafluorinated analogues"]}]}],"canonical_facts":{"dc:contributor.advisor":["Linclau, Bruno"],"dc:creator":["Brown, Kylie J."],"dc:date":["2011-04-26"],"dc:date.issued":["2011-04"],"dc:description.abstract":["A novel synthesis of the 2-deoxy-2,2-difluorocytidine nucleoside analogue gemcitabine has been achieved. Starting from the known 3,5-O-dibenzoyl-2- deoxy-2,2-difluororibose, the nucleobase moiety is constructed in a linear fashion, using amino- or urea glycosylation methodology. This methodology has also been employed to synthesise nucleosides containing a tetrafluorinated ribose sugar and has been compared to conventional convergent nucleobase introduction methods. In this respect, a high-yielding Mitsunobu-based protocol has also been developed. Both purine and pyrimidine analogues have been synthesised. The aminoglycosylation methodology has been investigated with a range of amines. The methodology proves high-yielding for primary amines and lesshindered secondary amines. In contrast to expectations, their stability in acidic media was not very high. Anomerisation and ring isomerisation studies have been conducted"],"dc:format":["text"],"dc:identifier.uri":["https://eprints.soton.ac.uk/193063/1/Kylie_Brown_PhD_Thesis.pdf"],"dc:publisher.department":["Chemistry (pre 2011 reorg)","Chemistry"],"dc:publisher.institution":["University of Southampton"],"dc:relation.isreferencedby":["https://eprints.soton.ac.uk/193063/"],"dc:title":["Synthesis of gemcitabine and it's tetrafluorinated analogues"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["doctoral"],"dc:type.qualificationname":["Ph.D."]},"updated_at":"2026-07-24T04:36:28Z"}