Total Syntheses of Andirolide N, Xylogranatopyridine B, and Granatumine A. [electronic resource].

9780438973343

Ann Arbor : ProQuest Dissertations & Theses, 2018.

1 online resource (439 p.)

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Chapter one of this thesis discusses the biosynthesis, isolation, structural diversity and therapeutic potential of the limonoid natural products. This chapter also details the state-of-the-art in the total syntheses of limonoids, which primarily relies on linear polyolefin cyclizations. As a point of departure, a fragment based coupling approach is discussed as a strategy to quickly assembly the limonoid scaffold. Chapter two details the first application of a fragment coupling approach toward the synthesis of the limonoid natural products. Andirolide N and a related limonoid congener, 8a-hydroxycarapin were quickly accessed through the strategic use of a degraded limonoid, iso-odoratin. Employing iso-odoratin allowed for late-stage installation of the challenging A-ring architecture present in andirolide N. The final step of this route demonstrates the chemical feasibility of our biosynthetic proposal that andirolide N arises from 8α-hydroxycarapin. The completion of these syntheses necessitated the development of several methodologies, such as ozonolytic β-fragmentation, the use of Gold's reagents for the preparation of enaminones and a copper-catalyzed aerobic γ-hydroxylation of carbonyl compounds. The third chapter pertains to the total synthesis of the limonoid alkaloids, which are proposed to arise biosynthetically from a mexicanolide-type limonoids, such as 8ahydroxycarapin. The total synthesis of xylogranatopyridine B relied on a convergent stannyl-Liebeskind pyridine synthesis to forge the central pyridine ring. The stannane fragment was prepared by a novel allyl-palladium catalyzed oxidative β-stannylation of enones. Additionally, the synthesis of the challenging bislactone lirnonoid alkaloids relied on a unique pyran to pyridine interconversion.

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August 21, 2019

Thesis (Ph.D.)--Yale University, 2018.

Yale University.