Date of Thesis

2016

Description

Bile acids are natural products that are located within a variety of organisms through metabolism of cholesterol. The less common allo bile acids contain a trans AB ring fusion and are designated as the C5α diastereomers. Although Iqbal, and Tochtrop have described synthetic approaches to the 5α stereocenter, there still remain issues of stereoselectivity and chemoselectivity when forging the AB trans ring. We have established a general approach to the synthesis of allo bile acids by applying a recently developed manganese catalyzed hydrogen atom transfer reduction. This key tactic enabled us to successfully synthesize allolithocholic acid over seven steps in 26% yield and 97% diastereomer purity, starting with the commercially available lithocholic acid. Notably, this is the first reported synthesis of allolithocholic acid. Derivatives of lithocholic acid were also synthesized to explore the hydrogen atom transfer reaction in order to develop an understanding of the reaction outcome in terms of stereoselectivity. Finally, this synthetic tactic was also applied to the synthesis of other allo bile acid derivatives such as deoxycholic, chenodeoxycholic, and hyodeoxycholic acids.

The later chapter in this thesis describes a synthetic endeavor to develop a general approach toward the eudesmane carbon skeleton through a double addition strategy. This strategy was effective in forming the C10 quaternary center and the C6–C7 bond in the eudesmane skeleton albeit with modest stereoselectivity as a 1:1 mixture of uncharacterized diastereomers.

Keywords

organic synthesis, bile acid, eudesmane, hydrogen atom transfer, stereoselective

Access Type

Masters Thesis (Bucknell Access Only)

Degree Type

Master of Science

Major

Chemistry

First Advisor

Michael Krout

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