Graduation Year

2011

Document Type

Dissertation

Degree

Ph.D.

Degree Granting Department

Chemistry

Major Professor

Bill Baker, Ph.D.

Committee Member

Abdul Malik, Ph.D.

Committee Member

Roman Manetsch, Ph.D.

Committee Member

Alberto van Olphen, Ph.D.

Keywords

organic chemistry, natural products, nudibranch, sponge, red alga, palmadorin, lectin, bioassay

Abstract

The marine realm and, in particular, the Antarctic benthos is largely unexplored and understudied. The chemical investigation reported herein reveals not only the biodiversity, but how that biodiversity manifests remarkable chemical diversity. In our continuing study of the nudibranch Austrodoris kerguelenensis, we have isolated a diverse suite of diterpenoid glyceride esters, palmadorins D - S (2.32 - 2.47), one of which is the first reported halogenated diterpene from a dorid nudibranch. Utilizing genomic data from collaborators, we have investigated the chemical diversity from phylogenetically unique specimens collected in close proximity to one another. Chemical groupings based on comparison of LC/MS metabolite fingerprints from individual organisms correlated well to the genetic data. Our research shows that A. kerguelenensis specimens from the same phylogroups elaborate near identical metabolite profiles to each other, but distinct from other phylogroups. Dendrilla membranosa is a dominant demosponge that prior studies have shown is rarely preyed upon and deters feeding against amphipods, the principal mesograzers of the Western Antarctic Peninsula. To assess the defensive nature of the pure compounds, artificial food pellets spiked with membranolides were evaluated in a feeding assay against the omnivorous amphipod Gondogeneia antarctica whereby only artificial pellets containing membranolide exhibited significant feeding deterrence. The research reported herein demonstrates that membranolides C and D were originally misassigned. Reevaluation of new extracts evolved additional fused furan membranolides G and H, and allowed for complete characterization of the four epimers. Extraction of sponge in CD3OD resulted in incorporation of a deuterated methyl group into fragment ions as evidenced from LC/MS chromatograms. Further chemical investigation of D. membranosa without the use of methanol revealed that these non-natural products arise from aplysulphurin, a known compound originally isolated from the sponge Aplysilla sulphurea, but later isolated from D. membranosa. These studies emphasize the importance of exploring the marine realm for the presence of antiviral compounds, not only for identification of small molecules but also as a source of potent macromolecules. Subfractions from Gigartina skottsbergii possesses strong anti-influenza activity toward both the A/Wyoming/03/2003 (H3N2) and A/California/04/2009 (H1N1) virus with EC50 values in the range of 5 to 10 μg/mL. The virus-inhibitory effect was selective, dose-dependent, strain-specific and the virus induced cytopathogenic effect (CPE) was reduced at non-toxic concentrations of the extract.

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