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Natural Products Analysis  of South Pacific Marine  Sponges

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thesis
posted on 09.12.2021, 09:44 by Taufa, Taitusi

This thesis describes the isolation and structure elucidation of 15 new secondary metabolites from Tongan and New Zealand marine sponges. A total of 18 sponge specimens were subjected to an NMR-based screening method, of which four were analysed in detail. Examination of a two-sponge association, Stelletta crater and Desmacella dendyi from New Zealand, resulted in the isolation of two new 4-methylenesterols, craterols A (94) and B (95). To the best of the author’s knowledge, compounds 94 and 95 represent the first secondary metabolites to be reported from either species. Both 94 and 95 possess a double bond between C-5 and C-6, a feature that is unprecedented in this subgroup of marine natural products. An investigation of a Tongan sponge Zyzzya fuliginosa afforded two new pyrroloquinoline alkaloids, 6-bromodamirone B (182) and makaluvamine W (183). Makaluvamine W (183) contains an oxazole moiety, which is uncommon in this group of natural products. Both 182 and 183 lacked activity against the human promyelocytic leukemia cells (HL-60). Five new compounds were isolated from a Tongan sponge of the genus Leucetta, including two glycerol lipids (238 and 239), three glycerol ethers (244–246) and an imidazole alkaloid (243). Naamidine K (243) is a new addition to the naamidine family, while the glycerol metabolites are non-imidazole alkaloid additions to the group of compounds reported from this genus. A spectroscopic investigation into the Tongan sponge Cacospongia mycofijiensis yielded four new zampanolide analogues (282–285) and a new oxygenated sesquiterpene, isodictyodendrillin A (280). The isolation of the zampanolide analogues gives insight into the structure-activity relationship (SAR) in this family of compounds. Zampanolides B–D (282–284) displayed potent antiproliferative activity towards HL-60 cell lines in the low nanomolar range (3–5 nM), while zampanolide E (285) was significantly less potent with an IC50 value of 306 nM. In addition, the re-isolation of dactylolide (281) and zampanolide A (278) from this sponge, established a firm conclusion regarding the controversial configuration of dactylolide (281), which possesses the same absolute configuration as (–)-zampanolide A (278) and has a levorotatory optical rotation.

History

Copyright Date

01/01/2018

Date of Award

01/01/2020

Publisher

Te Herenga Waka—Victoria University of Wellington

Rights License

Author Retains Copyright

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

Northcote, Peter; Keyzers, Rob