The synthesis of cell signaling molecules

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2021-12
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Alterman, Josh Louis
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Kraus, George A
Stanley, Levi
Winter, Arthur
Phillips, Gregory J
Venditti, Vincenzo
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Contents of the first chapter cover the synthesis of phenolic lipids which are naturally occurring in complex mixtures. Small variations between the substances make selective isolation difficult. Ginkgolic acid, an important constituent in ginkgo botanical elixirs, is one such chemical. Total synthesis is important for understanding its properties. An efficient route using cheap synthetic and bio-based synthons is detailed within, which allowed for the generation of ginkgolic acid and some related compounds in few steps. The second chapter covers a new synthesis for autoinducer-2, a small biologically important compound that is used in quorum sensing, a means of cellular communication. To help understand its role, a strategy was devised that recognized the highly functionalized nature of AI2 and its precursor. We developed an ozonolysis method to selectively generate diones from alkynes and led to a direct synthesis of AI-2. In the third chapter arylpropynes from the Sonogashira were explored. Benzofuranones could be provided via oxidation of the arylpropynes. Benzofuranone compounds are of agrochemical interest. As a result, they are interesting targets for organic synthesis. The volatile propyne required the development of new reaction conditions. A procedure with high atom economy and operational convenience was found. The process allowed easy installation of a propyne unit across electron withdrawing and electron donating aryl groups. Using this methodology, a direct synthesis of a benzofuranone was achieved utilizing the both the new Sonogashira conditions and the new ozonolysis conditions from chapter two. The fourth chapter discloses a new synthetic route to the pyoverdine chromophore and analogues. Pyoverdines are naturally produced by pseudomonads. The chromophore moiety is a component of the chelating affinity towards iron. Concise chemistry is still being explored, but a reasonable and straight forward synthetic route has been devised from azetidine ring chemistry.
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dissertation
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