Investigation of Marine and Terrestrial Natural Products

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This project focuses on the development of new methods for the synthesis of complex natural products. The synthesis and fragmentation of azabicyclic cyclopropylamines will be examined to evaluate these unusual compounds as novel chiral building blocks. A new reaction permitting the construction of the alkyl-aryl ether in cyclopeptide alkaloids will be utilized in the synthesis of ceanothine D, a cyclopeptide alkaloid that contains a chiral tertiary alkyl-aryl ether moiety. A copper and palladium-catalyzed approach for the synthesis of roquefortine C will provide this natural product, of great importance in food chemistry, in sufficient quantity to permit clarification of inconsistent toxicity data and establishment of the relationship of roquefortine C to oxaline. New coupling strategies effecting macrocyclization will be developed and applied to the synthesis of pondaplin, a strained [9]paracyclophane with labile functionalities. The synthesis of a new synthetically challenging natural product, trichodermamide A, will also be explored, permitting an assessment of the putative structure of penicillazine.With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Madeleine M. Joullie of the Department of Chemistry at the University of Pennsylvania. While natural sources provide many fascinating chemical compounds with promising biological activity, often they are available in insufficient quantities, derived from unreliable sources, and/or inappropriate as drugs due to undesirable side effects. Thus, the synthesis of complex organic chemicals "from scratch" is an essential endeavor. Professor Joullie and her students are developing novel methods, addressing unusual structural features, for the synthesis of complex natural products. Their targets include a novel compound, roquefortine C, that is of great importance in food chemistry, given its presence in blue cheese and inconsistencies in currently available toxicity data.