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Title: Studies towards the total synthesis of the brasilinolides
Author: Burton, P. M.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2010
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The brasilinolides, isolated from the culture broth of Nocardia brasiliensis, are a structurally unique family of immunosuppressive 32-membered macrolides. The northern portion of the brasilinolides is characterised by 11 contiguous stereocentres and requires differentiation of six secondary hydroxyls. Chapter 1 describes a scalable and efficient route to the C20-C37 hemisphere. The stereochemically dense C29-C37 fragment 56 was constructed employing highly stereocontrolled boron aldol reactions and subsequent hydroxyl-directed reductions. An olefination coupling of 56 with phosphonate 120 provided enone 119, which was then elaborated to the C20-C37 fragment 54. Overall, 54 was synthesised in 16 steps (longest linear sequence) and 13% yield from (S)-59. Chapter 3 describes two potential routes to the brasilinolide degradation fragment 31 via the synthesis of the advanced precursors 141 and 148. Finally, Chapter 5 includes model studies on the key C19-C20 bond formation during the pivotal fragment coupling of the two hemispheres of the brasilinolides. After considerable experimentation, the adducts 212 and 230 shown below were synthesised from truncated segments of the northern and southern hemispheres and their synthesis represent models from which to extend to the full hemisphere union.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available