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Natural products from some filamentous fungi and other sources

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thesis
posted on 27.03.2022, 21:50 by Nirmal Kumar Chaudhary
Natural products remain a major source for new drugs and drug leads owing to their unparalleled structural and chemical diversity and "drug-likeness" because of their evolutionary optimization to interact with living systems, unlike synthetic libraries. However, a combination of tedious isolation, repetitive isolation of known compounds, poor yields (supply) and structural complexities hindering total synthesis are some major bottlenecks in the process of drug discovery and development from natural products. Microorganisms offer a relatively unexplored source of new natural products by virtue of their vast biodiversity that can address the supply issue through fermentation. Moreover, microorganisms are amenable to selection and genetic manipulation for overproduction of the desired metabolite(s). The primary aim of this thesis is the isolation, characterization and biological screening of the secondary metabolites of some filamentous fungal species. Secondary metabolites of three filamentous fungi - Aspergillus banksianus, Aspergillus luteorubrus and Talaromyces stipitatus were characterized and screened. A total of 15 polyketide derived natural products were isolated from A. banksianus of which 10 were new metabolites. Among these, were the first isochromanone-orsellinic acid conjugates, isochromanone-anthraquininone conjugateand sulphur containing isochromanones including a rare sulfoxide metabolite. Chemical investigation of A. luteorubrus resulted in six metabolites including two new molecules, one was known but is a new natural product. Talaromyces stipitatus led to the isolation of 21molecules among which nine were new molecules. Among the new metabolites of T.stipitatus were 5 natural talauxins, which are condensation products of duclauxin with various L-amino acids. The semi-synthesis of new analogues of talauxins derived from D- and L-amino acids (except proline) and duclauxin is described. In addition, four new molecules from an Australian rainforest tree Galbulimima baccata were isolated and characterized. The structures of the isolated compounds were established by 2D NMR spectroscopy. Absolute stereochemistry of the isolated compounds was determined based on optical rotations, ECD, NMR, molecular modelling and TDDFT calculations. Plausible biogenetic pathway leading to these secondary metabolites are proposed wherever possible which can help in the design of biomimetic synthesis of these compounds.

History

Table of Contents

Chapter 1. Introduction -- Chapter 2. Banksialactones and Banksiamarins : novel Isochromanones and Isocoumarins from a new Australian fungus, Aspergillus banksianus -- Chapter 3. Talauxins from Talaromyces stipitatus and the semi-synthesis of talauxin analogs from their common biogenetic precursor duclauxin -- Chapter 4. Structure revision of talaromycesone : a and new phenalenones and polyesters from Talaromyces stipitatus -- Chapter 5. Luteosteroside and luteolactones from a new Australian fungus, Aspergillus banksianus -- Chapter 6. Isolation and structure elucidation of new alkaloids from the tropical rainforest tree Galbulimima baccata -- Chapter 7. Summary and conclusion.

Notes

Thesis by publication. Includes bibliograpical references

Awarding Institution

Macquarie University

Degree Type

Thesis PhD

Degree

PhD, Macquarie University, Faculty of Science and Engineering, Department of Molecular Sciences

Department, Centre or School

Department of Molecular Sciences

Year of Award

2018

Principal Supervisor

Peter Karuso

Additional Supervisor 1

Andrew Michael Piggott

Rights

Copyright Nirmal Kumar Chaudhary 2017. Copyright disclaimer: http://mq.edu.au/library/copyright

Language

English

Extent

1 online resource (x, 325 pages) graphs, tables

Former Identifiers

mq:71336 http://hdl.handle.net/1959.14/1273312

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