Synthetic Studies Towards Periglaucines A, B, and Related Bioactive Hasubanans

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DESCRIPTION (provided by applicant): Nitrogen-bearing natural products comprise a large number of biologically active molecules, often serving as effective pharmaceuticals in the treatment of disease. Of these, the hasubanan alkaloids possess promising biological activity, exhibiting antihepatotoxic and analgesic properties. In addition, these alkaloids present an intriguing structural architecture characterized by a densely functionalized propellane core. As a result of their biological and structural features, the hasubanans are an attractive target for total synthetic endeavors. The goal of the proposed research is to complete the total synthesis of two members of the hasubanan alkaloids, periglaucines A and B. Key to our synthetic strategy is the development of a diastereoselective 1,2-addition of nucleophiles to quinone imines derived from a chiral auxiliary. The resulting aminodienone products are expected to serve as versatile building blocks in the preparation of more complex propellane alkaloids. By employing a unified synthetic strategy, it is expected that a variety hasubanan alkaloids and derivatives can be readily prepared. With synthetic access to such alkaloids, it will be possible to facilitate studies aimed at elucidating their biological pathways and to potentially develop novel, more potent natural products.