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UBC Theses and Dissertations

Total synthesis of micrococcin P1 Lefranc, David

Abstract

This thesis describes the total synthesis of the thiopeptide antibiotic micrococcin P1. It unambiguously elucidates its structure, which has been subject to controversy for over thirty years. The centerpiece of the route to the target molecule is a facile one-pot construction of the central thiazole/pyridine cluster developed in our laboratory. This highlyconvergent route entails a delicate Michael addition to yield a Hantzsch dihydropyridine intermediate, which undergoes further oxidation to the fully aromatised heterocycle. The synthesis was completed by the coupling of this core with a highly-modified sensitive peptide chain. The modular nature of the synthesis can also accommodate modifications for SAR studies, contributing thereby to the fields of medicinal chemistry, pharmacology, and microbiology. At a purely chemical level, we remain confident that this work will serve as a valuable guide in the elaboration of other members of the thiopeptide family.

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Attribution-NonCommercial-NoDerivatives 4.0 International

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