Research Interests
The goal of our research is to study the structural chemistry of naturally occurring compounds, and to understand how structure affects stability, reactivity, and biological activity. This approach has required a merging of experimental and theoretical tools typically applied to three areas of organic chemistry, i.e., organic synthesis, natural products chemistry, and medicinal chemistry. Our research projects often involve a combination of 1) the isolation of new organic entities, 2) the use of both spectral and chemical methods for elucidation of planar and three-dimensional structures, 3) the application of high-field NMR and molecular mechanics calculations to investigate special chemical properties such as conformational flexibility, and 4) organic synthesis to support proposed structural assignments and for the preparation of additional compound and analogs for biological evaluation and structure activity relationship studies. Assessment of a molecule's potential as a chemotherapeutic agent is undertaken in collaboration with pharmacologists.
Within this context, our current studies are focused in two areas: 1) the discovery of new biologically-active naturally natural products, and 2) the synthesis of biologically-active natural products and their structural analogs.
Discovery of New Natural Products:
Over the past nine years, we
have concentrated on the discovery of new compounds with potentially
useful biological activities from either marine macroorganisms,
such as sponges and ascidians, or marine microorganisms. Our recent
discoveries from marine invertebrates include the imidazole alkaloid
(2E,9E)-pyronaamidine
9-N-(methyl)imine
(1), the beta-carboline alkaloids didemnolines A-H (e.g., 2 and 3),
and polycyclic heteroaromatic alkaloids plakinidine D (4) and arnoamines A (5) and B (6).
From microorganisms, we have
discovered a series of cyclic depsipeptides (e.g., kailuin A, 7), several polyketide-derived
metabolites, including wailupemycin
A (8), and four
new quinones halawanones
A-D (9-12).
Organic Synthesis:
Our synthetic efforts are often driven by a need to confirm a proposed chemical structure, generate additional material to undertake or continue biological testing, or to produce structural analogs for structure-activity-relationship (SAR) studies. Our past synthetic targets include the DNA-damaging pentathiepin varacin (13) and the beta-carbolines didemnolines A-H. Our recent discovery that the marine macrolides laulimalide (14) and isolaulimalide (15) are Taxol-like microtubule stabilizing agents has led us to undertake their syntheses.
