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Title: Studies towards the total synthesis of heteroclitin F and taiwanschirin A, B, C, and D
Author: Haughey, Maxwell Brian
ISNI:       0000 0005 0291 7346
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2020
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This thesis initially describes model studies developed towards key structural fragments of the taiwanschirin family of natural products. Through the use of these models, an original approach was conceived to enable the installation of the (Z)-enone as a single diastereoisomer. This novel sequence has been successfully applied to a wide substrate scope including esters, amides, ketones and thioesters. Furthermore, these studies led to the assembly of the 8-membered ring in high yield, and we were delighted to observe the formation of the desired alkene as a single (exo)-diastereoisomer in 81% yield. Extensive investigations are described into the incorporation of the pyruvate functional group in model compounds. This group proved to be particularly challenging, however a breakthrough was obtained and this approach enabled the assembly of a model compound that incorporated both the pyruvate group and the (Z)-enone. With a method developed for the incorporation of the three contiguous stereocentres, in addition to the pyruvate functional group, presented herein is a novel approach towards the first total synthesis of the taiwanschirin family. Finally, an approach to the heterocyclic core was developed and the planned synthesis successfully completed up to step 16 inclusive of an anticipated 22 steps. To the best of our knowledge, this is the first work to investigate the total synthesis of this family of highly structurally complex natural products, and represents a significant advancement in this field of research. The taiwanschirins represent an extremely challenging and biologically significant family of targets in total synthesis.
Supervisor: Donohoe, Timothy Sponsor: GlaxoSmithKline
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Chemistry, Organic ; Synthesis