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Title: Studies towards the biomimetic synthesis of (±)-lindenatriene and related natural products
Author: Fenlon, Thomas
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2009
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Abstract:
The work described in this thesis is divided into two parts, both of which are related to the synthesis of lindenane sesquiterpenoid natural products. Shizukaol A 1, cycloshizukaol A 2 and trishizukaol A 3 represent three of many novellindenane bi-and trisesquiterpene natural products isolated from plants of the Chloranthus genus. Biologically, a number of monomeric and dimeric structures containing the lindenane skeleton have been shown to exhibit antitumor, hepatoprotective and tyrosinase inhibitory activities. It was proposed that the majority of dimeric and trimeric structures could be accessed biomimeticaUy from the as yet unisolated reactive intermediate lindenatriene 4, itself a possible biosynthetic oxidative product of lindenene 5, a natural product isolated from the taxonomically unrelated species Undera Strychnijolie. The first part of this project is concerned with the expedient total synthesis of (±)-lindenene 5 from Hagemann's ester 7 via a key intramolecular cyclopropanation reaction of diazoketone 6. Initial investigations into the cyclopropanation resulted in an unexpected sterochemical outcome, allowing the total synthesis of two diasteromers of (±)-lindenene 5: (±)-epi-lindenene and {±)-iso-lindenene. The total synthesis of (±)-lindenene 5 was finally achieved by the thermally induced olefin insertion of diazoketone 6, marking the first example of such an intramolecular cyclopropanation carried out in the absence of a transition metal catalyst, along with the first example of the synthesis of a lindenane natural product. The second part of the project describes the approaches towards the biomimetic conversion of {±)-lindenene 5 into {±)-l indenatriene 4. Model studies on the conversion of furans into decorated butenolide structures were then applied to lindenene systems with varying degrees of success. (±)-Undenene 5 was converted into several chlorantholactone natu ral products, postulated as biosynthetic oxidative intermediates en route to lindenatriene 4. Although lindenat riene 4 was not synthesised, valuable insight was gained into the reactivity of many of the butenolide intermediates, and future work in the area seems promising.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.606391  DOI: Not available
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