Synthetic Studies Toward the Total Synthesis of Enterocin

Author: Tao, Yujia

Year: 2023

Degree: Dissertation (Ph.D.)

Advisor: Reisman, Sarah E.

Committee Members: Stoltz, Brian M.; Arnold, Frances Hamilton; Fu, Gregory C.; Reisman, Sarah E.

Option: Chemistry

DOI: 10.7907/jdhq-sb66

Abstract

As part of a broader program aimed at the synthesis of complex and highly oxygenated natural products, we initiated a chemical synthesis of the natural polyketide enterocin. This dissertation will disclose our efforts to bridge that gap through the development of synthetic strategies for the total synthesis of the enterocin. The studies herein will address three unique strategies to access the tactical difficulties in the rich oxygenation patterns and caged core structure of enterocin. The program was first inspired by a SeO2 multioxidation reaction, and the methodology has been successfully applied to install bridgehead oxygenation patterns in enterocin. A strategy featuring a radical-polar crossover reaction as an annulation step to quickly construct the [3.2.1] bicyclic core of enterocin is detailed. Initial studies have successfully achieved the radical-polar crossover annulation reaction to forge [3.2.1]bicycles with bridgehead hydroxyl groups, and will guide the future development toward the total synthesis of enterocin. An intermolecular aldol approach will be discussed to address the challenge on pyrone installation and core structure synthesis. In summary, the development of an efficient and general approach will allow the development of novel reactions and a comprehensive evaluation of the potential of caged polyketides to serve as medicinally interesting molecules.

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