Date of Award

Spring 1-1-2018

Document Type

Thesis

Degree Name

Master of Science (MS)

First Advisor

Maciej A. Walczak

Second Advisor

Maciej A. Walczak

Third Advisor

Wei Zhang

Fourth Advisor

David Walba

Abstract

Thiopeptide antibiotics are members of the ribosomally synthesized and post-translationally modified peptide class of natural products. They contain a unique trisubstituted six-membered nitrogen ring decorated with azol(in)e heterocycles, dehydroamino acids, and a macrocyclic structure. Thiopeptides act by inhibiting the bacterial ribosome and have demonstrated potent activities against a wide range of Gram-positive pathogens.

This work describes the synthesis of the two key fragments used in our total syntheses of micrococcin P1 and thiocillin I. The “bottom” fragments were assembled through modification and coupling of amino acids as well as the use of a molybdenum catalyzed cyclodehydration of cysteine residue to form the unique thiazole which differs from micrococcin P1 and thiocillin I. The “top” fragment was constructed using a C-H activation as the first step, a molybdenum catalyzed cyclodehydration to install the second thiazole, and a Stille/Hantzsch strategy to install the final thiazole heterocycle. The studies that lead to the efficient syntheses of these two fragments is reported.

Share

COinS