Towards the Total Synthesis of 5β-Hydroxy-Cis-Dehydrocrotonin And Development of Novel Methodology in the Synthesis of Cis-Vinylstannanes and Cis-Vinylpinacolboronates

Paul Malek Mirzayans (2011). Towards the Total Synthesis of 5β-Hydroxy-Cis-Dehydrocrotonin And Development of Novel Methodology in the Synthesis of Cis-Vinylstannanes and Cis-Vinylpinacolboronates PhD Thesis, School of Chemistry & Molecular Bioscience, The University of Queensland.

       
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Author Paul Malek Mirzayans
Thesis Title Towards the Total Synthesis of 5β-Hydroxy-Cis-Dehydrocrotonin And Development of Novel Methodology in the Synthesis of Cis-Vinylstannanes and Cis-Vinylpinacolboronates
School, Centre or Institute School of Chemistry & Molecular Bioscience
Institution The University of Queensland
Publication date 2011-05
Thesis type PhD Thesis
Supervisor Dr Craig Williams
Proff James De Voss
Total pages 228
Total colour pages 6
Total black and white pages 221
Subjects 03 Chemical Sciences
Abstract/Summary Within the taxonomical ranks of flowering plants (angiosperms) the majority of the abundant clerodane natural products can be derived. The families of Euphorbiaceae and Labiatae are known to contain the more unusual 19-nor-clerodanes. Among these natural products a small group of biologically active compounds, the so called crotonins, are structurally related by a C-12-furan substituted C-9 spiro-γ-lactone moiety and the presence of four contiguous stereogenic centres. Despite their biological activity these 19-nor-clerodane natural products have received little synthetic attention to date. The author’s work describes the synthetic work towards 5-β-hydroxy-cis-dehydrocrotonin, isolated from the species C. Schiedeanus Schltdl. from the family of Euphorbiaceae. In this work a five step concise route to the 19-nor-clerodane core is described utilising a thermal 6π-electrocyclisation approach. A rare approach to a cis-vinyl stannane, required in the synthesis of the triene precursor, is shown to proceed via mono-Stille coupling of (Z)-1,2-bis(trimethylstannyl)ethene with the corresponding triflate. The stepwise synthetic manipulations of the crotonin core towards the introduction of the required stereochemistry is then accomplished via a [4+2]-cycloaddition of singlet oxygen followed by reduction of the resulting endo-peroxide. Selective elimination of one, out of two chemically equivalent hydroxyl moieties, is demonstrated with excellent regioselectivity following the introduction of the 5-β-hydroxy moiety. The reactivity of two advanced intermediates towards α-allylation in an attempt to introduce the spiro-centre contained within the spiro-γ-lactone moiety is also investigated. The synthetic challenges posed by this project forced the development of a novel approach towards the synthesis of cis-vinyl stannanes and cis-vinyl pinacolboronates from their corresponding alkynes and the strength of this methodology has been demonstrated herein. The methodology developed tolerates oxygen functionality and utilises the extremely stereoselective hydrotelluration-transmetallation sequence developed earlier in this field. Both aromatic as well as aliphatic alkynes afford the corresponding stannanes and boronates in an entirely cis-selective manner. Bis-stannanes and pinacolboronates have also been synthesised by this methodology, albeit with reduced yield.
Keyword 19-nor-clerodane
5-β-hydroxy-cis-dehydrocrotonin
6π-electrocyclisation
singlet oxygen
α-allylation
dibutyl ditelluride
radical
cis-vinyl stannanes
cis-vinyl pinacolboronates
cis-selective
mechanistic study
Additional Notes 49, 217-221.

 
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Created: Wed, 05 Oct 2011, 21:14:17 EST by Mr Paul Malek Mirzayans on behalf of Library - Information Access Service