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UBC Theses and Dissertations

Terpenoids from marine and terrestrial sources Craig, Kyle Sheldon

Abstract

Studies on the Indonesian sponge Hippospongia sp. led, via bioactivity-guided fractionation, to the isolation of six linear norsesterterpene carboxylic acids. Rhopaloic acids B (35) and C (36) were known, but rhopaloic acids D(37)-G(40) were novel in structure. These compounds are the first known natural product inhibitors of RCE-protease, an important new target in cancer therapy. [diagrams not included] Two investigations of weedy plants, Ambrosia artemisiifolia and Vernonia baldwinii, whose extracts showed activity in a cell-based assay for G2 checkpoint inhibitors, were undertaken. Six sesquiterpenes were isolated for each weed (41-46, 47 and related compounds, respectively). With respect to A. artemisiifolia, an additional four sesquiterpenes were semi-synthesized in an effort to understand the requirements necessary for biological activity. When 47 was hydrogenated under standard conditions it no longer contained an α-β unsaturated ester side chain and biological activity was lost. Sesquiterpenes 42-44 represent some of the first compounds known to be both G2 checkpoint inhibitors and antimitotic agents, while 47 has the ability to activate phosphorylation of nucleolin and tau, making it a potential tool for the study of Alzheimer's disease pathology. [diagrams not included] In our continuing investigations into the chemistry of the Caribbean octocoral, Erythropodium caribaeorum, two additional briarane diterpenes 48-49 were isolated. A novel erythrane diterpene 50 and two novel aquariane diterpenes 51-52 were also isolated. The aquariane skeleton appears to be derived via a vinylcyclopropane rearrangement of an erythrane precursor. [diagrams not included]

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