Open Access Te Herenga Waka-Victoria University of Wellington
Browse
thesis.pdf (17.22 MB)

Chemical Investigations of Pacific Marine Organisms

Download (17.22 MB)
thesis
posted on 2023-05-15, 23:18 authored by Joe Bracegirdle

This thesis describes a comparative study of three screening methods for the discovery of new marine natural products (MNP) from South Pacific organisms. Over the course of the study, 13 tunicates, one bryozoan and one red alga collected from the waters of the Kingdom of Tonga and New  Zealand were investigated. Bioassay, ¹H nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) were used to prioritise six organisms for investigation, which resulted in the isolation and characterisation of 16 new and 11 previously reported metabolites.    


An NMR–based spectroscopic screening protocol led to the isolation of  the new cyclic polyhalogenated monoterpene costatone C (46), isolated from a NZ red alga identified as Plocamium angustum, which showed moderate antibacterial activity. The absolute configuration of a previously reported and co–isolated bis–normonoterpene (47) was also deduced using Mosher’s method. The NMR screening protocol also  prioritised the Tongan bryozoan Nelliella nelliiformis, from which the nucleosides nellielloside A and B (61 and 62) were isolated and inspired the synthesis of congeners 66–69. All six compounds showed potent kinase inhibitory activity against a subset of disease–relevant kinases, with IC50 values determined to be in the nM range for GSK3A, MAPK14 and RSK2.    


An MS screening protocol was also employed utilising molecular networking through the GNPS platform. Of the eight tunicates examined, three were further investigated based on promising constellations in the network, and collectively led to the identification of 13 new compounds. A new aromatic ketone (28) was isolated from the NZ tunicate  Distaplia stylifera, while a comprehensive examination of a NZ Synoicum kuranui sample resulted in two new compounds, rubrolides T and U (110 and 111). The encrusting tunicate Didemnum ternerratum was the most fruitful organism examined in this work, resulting in the isolation of ten new and three previously reported lamellarin sulfates (147–151 and 153–156). The absolute configurations of atropisomers 148–151 were  determined by comparison of experimental and calculated ECD spectra. Compound 151 showed moderate cytotoxicity against HCT–116 cells.


This work illustrated the power of molecular networking as a screening tool when applied to the MNP field, particularly for the isolation new derivatives within a previously known family of compounds. It also suggested that the more traditional NMR spectroscopy–based screening protocol is still very useful as a standalone method when no comparative  standards are available. These complementary techniques should be used together to maximise new MNP discovery. 

History

Copyright Date

2020-01-01

Publisher

Te Herenga Waka—Victoria University of Wellington

Rights License

Author Retains All Rights

Degree Discipline

Chemistry

Degree Grantor

Te Herenga Waka—Victoria University of Wellington

Degree Level

Doctoral

Degree Name

Doctor of Philosophy

Victoria University of Wellington Item Type

Awarded Doctoral Thesis

Language

en_NZ

Victoria University of Wellington School

School of Chemical and Physical Sciences

Advisors

Keyzers, Rob; Owen, Jeremy