This thesis describes the development of methods and strategies inspired by three natural products: the well-known anti-malarial quinine, the ladder polyether adriatoxin B, and nosperin – a natural product with unprecedented combinations of biosynthetic origins.
Chapter 1 details a novel method for constructing highly functionalized quinolones by CH-bond activation. This short, efficient, and scalable synthetic route begin C-H activation of aromatic carbonyl with Ru catalyst, oxime formation, and Beckmann rearrangement initiated LA is developed. This new method can be applied to synthesis of complex natural product including quinolines or small molecules in drug discovery.
Chapter 2 investigates plans for a total synthesis of Adriatoxin B and methodologies for ladder polyether compounds. Specific developments include a Ti-based subunit coupling method for pyran containing compounds, a ring-expansion reaction from pyrans to the 7-membered ring (oxepane), and from an oxepane to an oxocane (8-membered ring). In addition a new route for the synthesis of the cis-1,3-dimethyl pyran ring found in polyethers has been developed.
Chapter 3 provides a full story of the total synthesis and structure assignment of nosperin. Nosperin, known as a metabolite in symbiosis of lichen (Peltigera membranaces) and microorganism (Nostoc sp. cyanobacterium), was initially reported in 2013 with two unassigned stereocenters. A highly convergent synthetic route for Nosperin and its diastereomers has been developed that proceeds in 18 steps longest linear sequence. This synthesis provides the absolute and relative stereochemistry of the natural product, includes a revision of relative stereochemistry in the proline domain, and establishes the stereochemistry of the polyketide domain.
|Advisor:||Phillips, Andrew J.|
|School Location:||United States -- Connecticut|
|Source:||DAI-B 76/07(E), Dissertation Abstracts International|
|Keywords:||Adriatoxin, Nosperin, Organic chemistry, Quinoline, Synthetic chemistry, Total synthesis|
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