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Title: New approaches towards the total synthesis of macrocyclic bisbenzyl natural products
Author: Murgues , Paul Gabriel
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2013
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The macrocyclic bisbibenzyls are a family of natural products generally extracted from species of liverworts. They have attracted considerable attention from synthetic chemists as they display an interesting array of biological activities. Furthermore, as each contains a strained cyclophane core, they present an interesting challenge to the synthetic chemist. Many total syntheses have been published, but to date no general strategy based on robust conditions has been established. The thesis describes our attempts to establish such an approach for the synthesis of the macrocyclic bisbibenzyl family of natural product. The discussion is divided in two independent parts. The first approach described sought to generalise an existing approach that had proven successful for the synthesis of a few macrocyclic bisbibenzyl natural products. A key of that strategy was the use of palladium-catalysed cross-coupling reactions to unite key fragments. The synthetic plan was redesigned for the general case and rationalised in light of difficulties reported in the existing literature. Over 20 potential coupling precursors were synthesised in a few high-yielding steps and their behaviour examined in Suzuki-Miyaura cross-coupling reactions using various reaction protocols. A suitable combination of precursors and catalyst was found to afford many of the desired biaryl products in high yields, though further investigation is required to advance these to the natural product targets. The second strategy was based on a bidirectional approach and a biomimetic ring closure. The synthesis of acyclic precursors by means of Sonogashira and Heck couplings gave disappointing results. The use of Wittig olefination provided an excellent synthetic route to the required bisbibenzyl macrocyclisation precursors. Alas, none of the envisioned macrocyclisation reactions succeeded.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available