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Studies towards the total synthesis of labiatin A

Carosso, Serena (2011) Studies towards the total synthesis of labiatin A. PhD thesis, University of Glasgow.

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Abstract

In this thesis, the studies towards the total synthesis of labiatin A using metal carbenoid transformations are described. An introduction to the metal carbenoids chemistry is reported. In particular the synthesis of -diazocarbonyl compounds and their metal catalysed decomposition to generate metal-stabilised carbenoids are described. Two metal carbenoid transformations are presented in particular, namely the C-H insertion reaction and the oxonium ylide generation-sigmatropic rearrangement sequence. These reactions were chosen because of their fundamental importance in our synthetic strategy. Other synthesis of related natural products accomplished by our and other groups are also reported. Our retrosynthetic analysis of labiatin A involving the use of two metal carbenoid transformations (C-H insertion and oxonium ylide generation-sigmatropic rearrangement sequence) is presented, followed by the synthesis of the two building blocks identified in the retrosynthesis. The problems met in the synthesis and the modifications apported to the original synthetic plan are reported. One point of difference was the choice of using iodide 7, instead of bromide 6, in the coupling with alcohol 5. The coupling reaction between the two building blocks and the synthesis of the first key α-diazocarbonyl compound 4 are described. The first key metal carbenoid transformation, the C-H insertion reaction, is presented and the subsequent functional group modifications of the key tetrahydrofuranone 8 are also described. The problems encountered in the following part of the synthesis resulted in the modification of the protecting groups strategy. In particular, the impossibility of selective removal of the PMB group from the primary alcohol resulted in the substitution of the two PMB groups with two TBS groups. The functional group modifications of compound 9, directed to the synthesis of the second key α-diazocarbonyl compound 10, are described followed by the second metal carbenoid transformation, the oxonium ylide generation-sigmatropic rearrangement sequence, which afforded the tricyclic core of the target molecule in an efficient way. The further elaboration of the tricyclic core 11 and the different attempts to complete the synthesis of the target molecule are reported. Finally the experimental procedures and selected spectra are provided.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: natural products, total synthesis, metal carbenoids, C-H insertion, sigmatropic rearrangement
Subjects: Q Science > QD Chemistry
Colleges/Schools: College of Science and Engineering > School of Chemistry
Supervisor's Name: Clark, Prof. J. Stephen
Date of Award: 2011
Embargo Date: 7 May 2014
Depositing User: Ms serena carosso
Unique ID: glathesis:2011-2570
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 28 Jul 2011
Last Modified: 10 Dec 2012 13:57
URI: http://theses.gla.ac.uk/id/eprint/2570

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