Chemistry

Upon rough chromatography, such as vacuum liquid chromatography (see the picture), active fractions of the extract are identified through our strong bioassay program. More sophisticated chromatographic techniques (such as HPLC) and further bioassays guide the chemists to the active natural product.

The next step in our research is to determine the structure of the compound. Occasionally, this is an extraordinarily difficult process (for example, see the structure of phormidolide below)1, requiring many months of effort and the excellent instrumental capabilities.

The principle structure elucidation tools are NMR spectroscopy (we use 300 MHz and 500 MHz instruments) and Mass Spectrometry (both LCMS and GCMS). Occasionally, the complex problems associated with structure elucidation of bioactive marine compounds have motivated us to develop and publish new techniques in NMR spectroscopy.

Occasionally we are inspired by the bioactivity of the natural product to take on a total synthesis of the molecule with the goal to provide sufficient amount of the material and to establish a synthetic route that would allow access to natural product analogues. Other times, we simply modify the natural product slightly by chemical processes. In designing analogues, we typically stay away from combinatorial approach and seek to use rational by focusing on the potential pharmacophores. Our strong collaborative network that gives us access to many different bioassays makes our analogue syntheses even more exciting.

References

1.     Williamson, R. Thomas; Boulanger, Anna; Vulpanovici, Alexandra; Roberts, Mary A.; Gerwick, William H. Structure and absolute stereochemistry of phormidolide, a new toxic metabolite from the marine cyanobacterium Phormidium sp. Journal of Organic Chemistry (2002), 67(23), 7927-7936.

2.     Williamson, R. Thomas; Marquez, Brian L.; Gerwick, William H.; Kover, Katalin E. One- and two-dimensional gradient-selected HSQMBC NMR experiments for the efficient analysis of long-range heteronuclear coupling constants. Magnetic Resonance in Chemistry (2000), 38(4), 265-273.

Contact

Mailing Address
Scripps Institution of Oceanography
9500 Gilman Drive, MC 0212
La Jolla, CA, 92093-0212  

Phone
Dr. Bill Gerwick: (858) 534-0578
Dr. Lena Gerwick: (858) 534-0566