We recently completed the first total synthesis of (+)-spongiolactone, a marine diterpenoid natural product isolated in 1986 by Sica and coworkers.<i> Given the presence of the tricyclic �-lactone core, embedded in an overall compact and stereochemically rich structure, we hypothesized that spongiolactone would display interesting cytotoxicity against human cancer cell lines. Along the way to this natural product, we also synthesized regio and diastereomeric 6,15-bis-epi spongiolactone. In collaboration with Professor Stephan Sieber (UT M�nich), we have begun to examine the bioactivities of spongiolactone, regioisomeric 6, 15-bis-epi spongiolactone, and simpler derivatives for the first time. Interestingly, the regio, diastereomeric natural product has shown the greatest cytotoxicity (10-20 �M) in this series thus far against human myelogenous leukemia cells: over a three-fold increase in potency compared to the natural product itself (70-80 �M). In this presentation, the synthetic details of spongiolactone-related compounds, including the synthesis of probes toward activity-based protein profiling, will be presented with a focus on the cytotoxicity studies that have since ensued.<i> Mayol, L.; Piccialla, V.; Sica, D. Tetrahedron Lett. 1987  , 28, 3601.

Probing the bioactivity of (+)-spongiolactone and related compounds

247th National Meeting (2014)

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