A unified strategy toward the biogenetically related oroidin derived bisguanidine marine alkaloids: Palau'amines, styloguanidines and axinellamines

Natural products that exhibit potent biological activity in conjunction with novel structural features constitute attractive synthetic targets. The oroidin-derived class of bisguanidine marine alkaloids including palau'amine (i), styloguanidine (iv) and their brominated congeners as well as the axinellamines (vii–x) share a complex polycyclic framework that features a densely functionalized cyclopentane core coupled with potent biological activity, which most notably include immunosuppressive, chitinase inhibitory and antibacterial activity, respectively.*; The overreaching goal of this research project was directed toward the development of a general and concise synthetic strategy, which would grant access to the spirocyclic core of this class of biogenetically related natural products. In this regard, our synthetic strategy was inspired by a biosynthetic proposal for palau'amine, featuring a Diels-Alder reaction and chlorination/ring contraction sequence as key synthetic transformations. The successful implementation of this strategy delivered the fully functionalized cyclopentane moiety embedded in spirohydantoin core xi. The intermolecular mode of chlorination furnished a spirohydantoin, which is epimeric at C5 relative to C17 in palau'amine and epimeric at C3 relative to C11 in axinellamine.*; *Please refer to dissertation for diagrams.