This research program deals with the stereospecific total synthesis of several complex naturally-occurring molecules having biological and/or structural significance. In particular, emphasis will be placed upon producing and refining methodology having potentially broad applicability which will be of practical use to both organic and medicinal chemists involved in synthesis of chemotherapeutic agents. Work has been initiated on total syntheses of some of the challenging, structurally unique polycyclic marine bryozoan alkaloids of the chartelline/chartellamide/securamine group and these studies will be continued during the requested grant period. Specifically, total syntheses of chartelline A and securine A/securamine A will be completed. In addition, studies are nearing completion on a short enantioselective total synthesis of the unusual Securinega alkaloid secu?amamine A via a novel tandem multistep process to construct the unique tetracyclic ring system of the natural product.
With this award, the Organic and Macromolecular Chemistry Program of NSF is supporting the research of Professor Steven M. Weinreb of the Department of Chemistry at Penn State University. Professor Weinreb's research efforts revolve primarily around the development of efficient new methodology for the synthesis of heterocyclic organic compounds, and applications of this chemistry to the synthesis of important structurally complex natural products. Successful development of the methodology will have particular impact on synthesis of intermediates in the pharmaceutical and agricultural industries.
Project Outcomes Steven M. Weinreb, PI NSF CHE-0806807 The primary objectives of this research program have been to develop a combination of novel synthetic methods and new strategies for the synthesis of bioactive heterocycles and alkaloid natural products. Emphasis was placed upon producing and refining methodology having potentially broad applicability which will be of practical value to both organic and medicinal chemists involved in synthesis of bioactive compounds. Pharmaceutical research and drug development has a multibillion dollar annual impact on the US economy, and its success is heavily dependent on this kind of synthetic methodology provided by academic laboratories such as ours. In addition, studies were conducted on target oriented total syntheses of a number of structurally unique and complex nitrogen-containing natural products. For example, during the last grant period we have completed and published the first total synthesis of the unique alkaloid secu’amamine A via a novel strategy, which also confirmed the structure and absolute configuration of the molecule. Moreover, a novel total synthesis has been completed of one member of the communesins, a small but structurally unique family of fungal metabolites, some of which have been found to have significant biological activity, including insecticidal and anticancer properties. This grant has also provided practical training for M.S. and Ph.D. students in sophisticated synthetic organic and heterocyclic chemistry. The young scientists trained under this NSF grant will eventually take research positions in the chemistry industry, most often in pharmaceutical or other health-related corporations, thereby having an important economic impact as well as providing significant health benefits to the populations of the US and the world.
