Total syntheses of (+)-lyconadin A and (-)-lyconadin B

The dissertation contained herein describes studies concerning the total syntheses of (+)-lyconadin A and (-)-lyconadin B, as well a model studies designed to evaluate late-stage alpha-pyridinone and dihydropyridinone anullation strategies. Chapter 1 describes a general introduction to the lyconadins, including their isolation, biological evaluation and proposed biosynthesis. Chapter 2 describes the retrosynthetic analysis, construction of ketone (+)- 47, evaluation of model fragment coupling strategies, construction of the piperidine alcohol (+)-45, fragment coupling and conjugate addition reaction studies that led to the tricycle (-)-100.*; Chapter 3 details the correction of the C(12) stereochemistry, attempts at direct formation of the N-C(13) bond, examination of an unsuccessful epoxide-based strategy toward formation of the tetracyclic core and then examination of a successful olefin iodoamination-based strategy directed toward tetracyclic ring formation, which led to the tetracyclic ketone (-)- 34. As a result of difficulties encountered in implementing a one-step alpha-pyridinone ring forming reaction, model studies were carried out to evaluate a novel alpha-pyridinone ring-forming strategy. Upon completion of the model studies, the developed strategy was then applied to the total synthesis of (+)-lyconadin A ( 1). Modification of reaction conditions then allowed for the successful construction of (-)-lyconadin B.; *Please refer to dissertation for diagrams.