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cyclobutadiene cycloadditions with imines
[2+2+1] Cycloadditions
Cacospongionolide B
5-8-5 Ring Systems
5-7 Ring Systems
Tandem Methathesis Olefin Isomerization
Catalytic Asymmetric Synthesis of Amines



Researchers - Rebecca Casaubon, Krista Granger

The basis of my graduate research has been the use of organic synthesis to study biological interactions.  Ilimaquinone (1) is a marine sponge metabolite with a wide range of biological activities including antiviral, antiinflammatory,  antimicrobial, and antimitotic effects.  In 1993, Malhotra et al. showed that 1 impedes cellular protein trafficking events by reversibly breaking up the Golgi apparatus into vesicles. This activity gives us an opportunity to use ilimaquinone and analogs as probes of intracellular vesicle-mediated protein trafficking, which could lead to the development of specific inhKrista Grangeribitors of these processes and may even have implications in antiviral and anticancer treatments. Affinity chromatography, photoaffinity, and fluorescence microscopy studies using active ilimaquinone analogs (e.g. 2-4) have implicated enzymes of the cellular activated methyl cycle, particularly S-adenosylhomocysteine hydrolase, as targets of ilimaquinone.1

In conjunction with the ilimaquinone study, and to gather more information about the mechanisms behind these biological activities, we have begun studies toward the total synthesis of norrisolide (5). Norrisolide was isolated in 1983 by Faulkner, Clardy and coworkers in a study of the chemical defense system of nudibranch molluscs and has also been reported to vesiculate the Golgi apparatus.  However, unlike the case of ilimaquinone, vesiculation by 5 is irreversible.  A convergent synthetic route will allow for synthesis of analogs that can be used to determine the biological interactions of the natural product.  It will be particularly interesting to determine if 1 and 5 share the same or related biological targets.


1(a) “Interactions of (-)-Ilimaquinone with Methylation Enzymes: Implications for Vesicular-Mediated Secretion.”  Radeke, H. S.; Digits, C. A.; Casaubon, R. L.; Snapper, M. L.  Chem. Biol., 1999, 6, 639.  
 (b) “ S-Adenosylmethionine Reverses Ilimaquinone’s Vesiculation of the Golgi Apparatus: A Fluorescence Study on the Cellular Interactions of Ilimaquinone.”  Casaubon, R. L.; Snapper, M. L.  Bioorg. Med. Chem. Lett., 2001, 11, 133.

Merkert Chemistry Center, Rms 337 & 339
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