Natural products--Synthesis

Nature has served human kind m many ways, one of which is a source of
medicines. Natural products from marine sources represent a relatively new area
of research and have shown tremendous potential as a source of new chemical
entities in drug discovery. Caribbean gorgomans corals of the genus
Pseudopterogorgia have been shown to produce a variety of chemically
interesting and biologically significant secondary metabolites. ln this dissertation,
the Caribbean coral Pseudopterogorgia acerosa has been investigated for the
presence of novel diterpenes and these compounds were found to belong to three
different classes: pseudopteranoids, bis-pseudopteranoids and lipidyl
pseudopteranes. Nine of these were new compounds. The structural elucidation of these compounds was performed using spectroscopic means such as l D and 20
NMR, and mass spectroscopy.
There is growing evidence that secondary metabolites isolated from manne
invertebrates may actually be produced by a bacterial symbiont. The research
studies in our laboratory regarding the source of diterpenes in the selected
gorgonian corals suggested a bacterial origin. The hypothesis that coral associated
bacteria are the source of diterpenes in the coral P. acerosa, was evaluated using
the series of experiments and evidence supported this biosynthetic origin.
A study comparing the "gall" tissue and healthy coral tissue in terms of diterpene
content and culturable bacterial communities showed that different groups of
diterpenes were concentrated in different coral tissue types. It was also observed
that the bacterial populations associated with the "gall" and healthy tissues were
considerably different. Furthermore, observed specificity in antimicrobial activity
of certain groups of compounds against bacteria isolated from the same coral
suggested the ecological role of these compounds. This work with "gall" tissue
supports the hypothesis that diseased coral tissue represents an excellent source of
bioactive natural products for drug discovery.
Additionaly, a simple LC-MS method was developed for the analysis of
anticancer drug carmustine in plasma.

The marine environment has proven to be an extremely rich source of novel natural products with activities in a variety of biological assays. The field of marine natural products chemistry has enjoyed an explosion of growth over the past 40 years and currently there are marine-derived metabolites in clinical trials for cancer, analgesia, allergy and cognitive diseases. Even with this tremendous development, it is clear that chemists and pharmacologists are only beginning to scratch the surface of the biomedical potential of marine organisms. One problem with this source of new pharmaceuticals is that the supply of such compounds can be problematic. The thesis describes projects directed at fundamental biosynthetic questions regarding terpenes from marine corals. In a general sense, these projects are directed as addressing the supply issue identified above. One project examined the origin of terpene building blocks in the coral Pseudopterogorgia elisabethae. A second project focused on the characterization of terpenes from Leptogorgia minimata. Here, a new cembranoid diterpene was isolated. Experiments were also conducted to identify a microbial source of terpene biosynthesis in this system. Data strongly supported a bacterial origin of these compounds.