Graduation Year

2006

Document Type

Dissertation

Degree

Ph.D.

Degree Granting Department

Chemistry

Major Professor

Bill J. Baker Ph.D.

Keywords

Antarctic tunicate, Palmerolide macrolide, Cytotoxicity, Nudibranch, Palmadorin

Abstract

Synoicum adareanum is a colonial tunicate commonly found on the benthos around Palmer Station on Anvers Island, Antarctica. A comprehensive chemical investigation of the lipophilic extract of the frozen tunicates gave a new series of polyketide macrolides, palmerolides A-E and H. The structure elucidation of these compounds was accomplished by extensive NMR and mass spectral studies.The palmerolides are unusual 20-membered macrolides displaying functionality more commonly found in sponges or cyanobacteria. Palmerolide A, the major member of the group, shows significant and selective in vitro cytotoxicity against melanoma with three orders of greater sensitivity relative to other cell lines tested, in the National Cancer Institute (NCI) 60 human cancer cell-line panel. In addition, it displays potent cytostatic activity against several other cancer cell lines. Based on NCI's COMPARE analysis, palmerolide A was investigated as a V-ATPase inhibitor and shown to bind the V0 subunit with 2 nM inhibition.Austrodoris kerguelenensis is a common Antarctic nudibranch widely distributed in the High Antarctic and Sub Antarctic Zone. It is characterized by the presence of terpenoid glyceryl esters which are supposed to be involved in defense. Chemical investigations of several specimens of A. kerguelenensis collected near Palmer station Antarctica afforded hitherto undescribed series of clerodane diterpenoid glycerides. The structure elucidation of three major compounds of this series, palmadorin A, B and C was accomplished.

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