Author: Patryk Syta
Syta, Patryk, 2020 Synthetic studies towards Nocapyrone and Violapyrone natural products, Flinders University, College of Science and Engineering
Terms of Use: This electronic version is (or will be) made publicly available by Flinders University in accordance with its open access policy for student theses. Copyright in this thesis remains with the author. You may use this material for uses permitted under the Copyright Act 1968. If you are the owner of any included third party copyright material and/or you believe that any material has been made available without permission of the copyright owner please contact copyright@flinders.edu.au with the details.
This doctoral thesis documents the investigation of stereocontrolled total synthesis of Nocapyrone and Violapyrone pyrone containing natural products. These independently isolated polyketide natural product families shared structural features, including pyrone cyclisation modes with C-6 substitution. From the natural product families 2 natural products, Violapyrone I and Nocapyrone H, and 2 natural product stereoisomers, Violapyrone E isomer and (−)-Nocapyrone C, were synthesised.
Building upon previous research from 2013 in the Perkins group, two synthetic strategies were investigated in the pursuit of Violapyrone E and Nocapyrone C natural products. The first generation synthetic strategy investigated the application of a convergent approach through early-stage pyrone preparation and side-chain coupling. The strategy was ultimately unsuccessful in realising the crucial coupling step between pyrone and side-chain fragments. The second-generation synthetic strategy investigated a linear approach, building the side chain up from asymmetric Crimmins aldol fragment and utilising late-stage pyrone preparation. This second-generation strategy was able to provide the natural products, Violapyrone I and Nocapyrone H, and stereoisomers, Violapyrone E isomer and (−)-Nocapyrone C. Analytical spectroscopic data was able to provide the evidence for the assigned characterisation.
This thesis also investigated the potential of preparing the α-methoxy-γ-pyrone synthon through the desymmetrisation of α,α'-dimethoxy-γ-pyrone. The preparation of α,α'-dimethoxy-γ-pyrone and desymmetrisation to α-methoxy-γ-pyrone previously demonstrated by De Paolis and co-workers was refined through intensive reaction screening and developed into a more robust protocol.
Keywords: Pyrones, Natural products, Total synthesis, Polyketides, Aldol, Asymmetric synthesis, Nocapyrone, Violapyrone
Subject: Chemistry thesis
Thesis type: Doctor of Philosophy
Completed: 2020
School: College of Science and Engineering
Supervisor: Michael Perkins