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The enantioselective total syntheses of eight cladiellin natural products

Berger, Raphaëlle (2011) The enantioselective total syntheses of eight cladiellin natural products. PhD thesis, University of Glasgow.

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Abstract

The cladiellins (also known as eunicellins) are oxygen-bridged 2,11–cyclised cembranoids, isolated from gorgonian octocorals and soft corals. They present an unusual oxatricyclic ring system composed of a hydroisobenzofuran and an oxonene unit. The natural role of these cembranoids is proposed to involve predatation deterrence, and biologically they have been shown to exhibit in vitro cytotoxicity against various cancer cell lines, anti inflammatory properties antimicrobial activities. The Clark group has been interested in the synthesis of cladiellins for some time, and in 2007 Clark and co-workers reported the total synthesis of vigulariol. This thesis describes the investigation of the synthesis of both E- and Z-cladiellins using our general strategy. The key transformations in the synthetic route are ring formation reactions. Firstly, a SmI2-mediated reductive cyclisation forms the tetrahydropyran ring, then a tandem oxonium ylide formation [2,3]-sigmatropic rearrangement constructs the oxabicyclo[6.2.1]undecenone bicyclic core. Finally, a Diels-Alder cycloaddition reaction forms the third ring of the tricyclic core of the cladiellins. Particular interest was given to the tandem oxonium ylide formation [2,3]-sigmatropic rearrangement reaction. This transformation was studied in order to develop conditions allowing the selective formation of the E-oxonene ring needed for the synthesis of the E-cladiellin tricyclic core. Herein, is presented work towards the synthesis of ophirin B, a cladiellin bearing a Z-oxonene alkene, as well as the enantioselective total synthesis of eight cladiellins obtained from an E-cladiellin tricyclic core: (−)-cladiella-6,11-dien-3-ol, (−)-cladiell-11-ene-3,6,7-triol, (−)-3-acetoxycladiella-6,11-diene, 3-acetoxy-cladiellin-11-ene-6,7-diol, (−)-sclerophytin A, (−)-sclerophytin B, (+)-deacetylpolyanthellin A and (+)-polyanthellin A in 20 to 24 steps from our allylic alcohol precursor.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Total synthesis, Cladiellin, natural product
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
Depositing User: Miss Raphaelle J Y Berger
Unique ID: glathesis:2011-2565
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 11 May 2011
Last Modified: 10 Dec 2012 13:57
URI: http://theses.gla.ac.uk/id/eprint/2565

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