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Title: Synthesis and biosynthetic studies of heterocyclic metabolites
Author: Battaglia, Ugo
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2012
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Heterocyclic compounds play an important role in many biological processes due to their versatility. Amongst these, indole alkaloids and purines represent two major classes of biologically active heterocyclic compounds, which are discussed further. First, the total synthesis of the marine triazolopyrimidine essramycin is presented. The synthesis proceeded in two steps and confirmed the structure initially proposed when the metabolite was isolated from the Mediterranean Sea. The family of dilemmaones, isolated from the South African coast of Cape Town, shows high similarity with previously isolated marine indole alkaloids, such as trikentrins and herbindoles. Their structure was elucidated only through spectroscopic studies. Here we present the first total synthesis of dilemmaone B and confirmation of its proposed structure. The last part of this work concerns 7 -deazapurines. These compounds, although well known in transfer RNA and in several nucleoside antibiotics isolated from Streptomyces sp., have been shown to be involved in many important biological processes. A fundamental point in their biosynthesis has not been completely elucidated yet, i.e. the loss or rearrangement ofN-7 in the purine precursor. Having prepared a novel doubly labelled purine, [2_13C, 7-15N]-adenine, we used it as a biosynthetic precursor to toyocamycin. NMR and mass spectrometry showed incorporation of 13C but loss of 15N in the toyocamycin derived from our fermentation. These findings, in combination with recent results obtained by McCarty et al., allow a chemical mechanism for the loss of N - 7 in 7 -deazapurine biosynthesis to be formulated for the first time. Finally, synthesis of the biosynthetic precursor, 6-carboxy-5,6,7,8- tetrahydropterin, and construction of a model system for a mechanistic study are presented herein.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available