Synthetic and biosynthetic studies on phomoidrides /
Phomoidrides are fungal secondary metabolites belonging to the nonadrides family of natural products and they display important squalene synthase and farnesyl transferase inhibition properties. The first chapter of this dissertation gives a broad introduction to the nonadrides, with particular emph...
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| Format: | Thesis Book |
| Language: | English |
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[Place of publication not identified] :
[publisher not identified] ;
2001.
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| Subjects: | |
| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=726103911&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | Phomoidrides are fungal secondary metabolites belonging to the nonadrides family of natural products and they display important squalene synthase and farnesyl transferase inhibition properties. The first chapter of this dissertation gives a broad introduction to the nonadrides, with particular emphasis to their common biosynthetic pathway explored by Sutherland's pioneering work and the few total syntheses existing to date. In the second chapter we introduce our biosynthetic proposal, elaborated on the basis of Sutherland's work, entailing the homodimerisation of two maleic anhydride derivative subunits to afford the fully functionalised phomoidrides core structure. Classical feeding studies using ¹³C labeled acetate and succinate derivatives and whole cell cultures of the producing fungus (ATCC 74256) are described in the third chapter. These experiments enabled us to determine the biosynthetic origin of all the carbons in the phomoidride structure. In order to shed light on the proposed homodimerisation pathway, the ²H labeled maleic anhydride monomer was synthesized and fed to the culture of the microorganism. Deuterium label incorporation in the resulting phomoidride B strongly supports our biosynthetic hypothesis and paves the ground for a possible biomimetic synthesis of these molecules. A biomimetic approach to the synthesis of the phomoidrides is explored in Chapter IV, where a library of potential cyclisation substrates is synthesized and tested in a one-pot combinatorial format. |
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| Item Description: | Vita. "Major Subject: Chemistry". |
| Physical Description: | xi, 173 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilm Inc. |
| Bibliography: | Includes bibliographical references (leaves 87-91). |