SYNTHESIS OF MARINE DERIVED MACROCYCLIC SALICYLATES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Natural products that elicit a specific biological response represent unique tools to identify, study, and target possible new gene products. Part of this research program is directed towards the design and synthesis of natural products that have unique actions on mammalian cells. In this context, we are developing a versatile total synthesis of salicylhalamides A-B and lobatamides A-F. These marine-derived macrocyclic salicylates represent a potentially new mechanistic class of antitumor compounds, and warrant the development of probe reagents for mechanism of action studies. In addition, only trace quantities of these secondary metabolites can be obtained from their natural source and neither these, nor any structurally related compounds, have been synthesized previously. An active interplay between chemical synthesis and cellular assays will pave the way for lead optimization efforts and an affinity-based search for the natural product's biological target.