University of Tasmania

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Studies on the synthesis of biologically active, small molecule natural products

posted on 2023-05-26, 17:09 authored by Molesworth, PP
Common potato scab affects potato farmers worldwide and costs the Tasmanian potato farming industry approximately $5 million dollars a year. The disease is caused in white potatoes by the common soil bacterium streptomyces scabies, from which several secondary metabolites have been isolated; these are known as the thaxtomin class of phytotoxins. These compounds have been shown to cause scabs in potatoes in sterile conditions and are phytotoxic to cellulose based plants. Several approaches to the total synthesis of the thaxtomins have been investigated. The most successful proceeds via the synthesis of 4-nitrotryptophan, followed by peptide coupling and cyclisation to give two of the three dehydroxy-thaxtomins. Other routes starting from glycine anhydride using condensation chemistry to build the three ring system have provided a series of analogues for structure activity testing. Toxicity of the analogues and synthetic thaxtomins has been analysed using Arabidopsis thaliana. Two analogues showed activity approaching thaxtomin A and show promise as potential new herbicides. Non-toxic analogues have been tested for their ability to ameliorate or negate the effects of thaxtomin A using a variety of models. These compounds provide a possible solution to the scab problem. Current methods for the synthesis of the pyrrolidine antibiotic anisomycin are complicated and rely on the preparation of a 3-pyrroline intermediate. Two novel methods to target this advanced intermediate are discussed, firstly use of a Zn/HCI reduction of a a-ketopyrrole, and secondly the reduction of N-tosyl pyrroles with TFA/NaCNBH3 . The use of N-toysl protected 3-pyrrolines as building blocks towards hydroxyl substituted pyrrolidines is also explored. Synthesis of gram quantities of the C19 and C21 triene sex pheromones of the autumn gum moth (Mnesampe/a private) has proved difficult because of the tendency of the trienes to decompose through auto oxidation. We present an approach to the synthesis of these compounds by spiking the starting material with the antioxidant BHT and carrying it through the reaction scheme. This enables a significant improvement in the overall yield of the desired product, which increased from 20% without the antioxidant to 86% with.


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Copyright 2010 the author Thesis (PhD)--University of Tasmania, 2010. Includes bibliographical references. Ch. 1. Synthesis of thaxtomin compounds and analogues -- Ch. 2. Biological testing of thaxtomins and thaxtomin analogues -- Ch. 3. Using pyrrole as a template to prepare anisomycin -- Ch. 4. Improving the synthesis of pheromone components of the Autumn Gum moth

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