Total Synthesis of Tetrahydrofuranol-Containing Natural Products and Studies Toward Eleutherobin

Date created: 
Natural products
Total synthesis
Laurefureynye A
Coniothyrinone D

An extension of previously developed methodology towards the synthesis of tetrahydrofuranol rings is demonstrated in the total synthesis of amphirionin-4 in 11 steps comprising the first total synthesis of this natural product. Furthermore, we were able to exploit this methodology toward the total synthesis and structural reassignment of laurefurenyne A. The development of a flexible and concise synthesis allowed for access to the proposed stereostructure of the natural product and, following analysis of spectral data, indicated this structure had been misassigned. Further synthetic efforts completed the synthesis of the correct structure of laurefurenyne A and enabled investigations into the biosynthesis of this natural product. An additional study describes efforts toward the synthesis of the promising anti-cancer natural product eleutherobin. As part of these efforts we have developed a cyclobutanone α-arylation/ring expansion strategy that affords access to α-tetralones. This methodology has been expanded toward the synthesis of a wide range of α-arylcyclobutanones and α-tetralones including the incorporation of heterocycles. Our efforts towards the synthesis of the core of eleutherobin through an α-tetralone intermediate are detailed including a radical cyclization method to form a vital C-C bond required for a proposed retro-aldol fragmentation. Furthermore, we have exploited this approach in our efforts toward the total synthesis of coniothyrinone D. While ultimately unsuccessful in accessing the natural product, this synthesis has demonstrated the utility of this approach towards the synthesis of this natural product scaffold.

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This thesis may be printed or downloaded for non-commercial research and scholarly purposes. Copyright remains with the author.
Robert Britton
Science: Department of Chemistry
Thesis type: 
(Thesis) Ph.D.