Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.780409
Title: Synthetic studies towards aruncin B : total synthesis, structural revision and synthesis of analogues for biological evaluation
Author: Ribaucourt, Aubert
ISNI:       0000 0004 7966 0537
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2017
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Abstract:
This thesis describes synthetic studies towards the recently isolated and previously unsynthesised cytotoxin aruncin B, a small molecule inhibitor of the Bcl-2 family antiapoptotic proteins. An initial approach relying on an Achmatowicz reaction is first presented. This method was unsuccessful. An alternative approach relying on a RCM / ethoxyselenation-selenoxide elimination was then envisaged. This method successfully delivered the Na salts of the Z- and E- isomer of the originally proposed structure of aruncin B, along with a third closely related isomeric Na salt. The free acids could not be obtained from these salts, suggesting structural misassignment of aruncin B. An alternative g-alkylidenebutenolide structure is proposed, and its synthesis using a related RCM / hydroxyselenation-selenoxide sequence is presented. This sequence confirmed the true structure of aruncin B, but suffered from reproducibility issues. An alternative sequence based on b-iodo MBH followed by Sonogashira cross-coupling-5- exo-dig-lactonisation was successfully applied to the synthesis of the true structure of aruncin B, as well as 15 analogues for biological evaluation.
Supervisor: Hodgson, David M. Sponsor: People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.780409  DOI: Not available
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