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Title: Total synthesis and SAR of thapsigargin and related analogues and mechanistic studies of perovskite-mediated Suzuki reactions
Author: Andrews, Stephen Phillipe
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2007
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This thesis is divided into two broad categories: the synthesis and SAR of thapigargin I and related derivatives, discussed in Part A, and mechanistic studies of perovskite-mediated Suzuki reactions, discussed in Part B. Experimental procedures for both projects can be found in Part C, along with appendices and references. (Fig. 566401A) Part A delineates the successful synthesis of unnatural analogues of thapsigargin 89, 91 and 93, which were subsequently evaluated as SERCA inhibitors. The results show that unlike the related analogue 33, none of these analogues significantly inhibited SERCA. (Fig. 566401B) Degradation studies of a natural sample of thapsigargin 1 are also described. the intermediates obtained were used to probe possible reactions, conditions and protecting groups for the final steps of the total synthesis of the natural product and served to highlight problems with other synthetic routes. Discussion of how these results were successfully applied to the completion of the first total synthesis of thapsigargin can be found in Section 2. Part B describes work conducted during the first year of these graduate studies and many of the results have now been published. A battery of experiments was used to convincingly show that LaFe0.57Co0.38Pd0.05O3-mediated Suzuki reactions take place, in part at least, via solution-phase Pd intermediates, believed to desorb from the perovskite lattice during the reaction and be recaptured at the end of the cycle. A series of related structures have been evaluated as potential Suzuki catalysts and their structures and activities are critically assessed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available