Concise total synthesis of (±)-Dibromoagelaspongin

Marine alkaloids containing a diaminoimidazole-derived core possess intriguing chemical structures and have displayed promising antimicrobial activity in preliminary screens. However, the synthesis of these compounds has been hindered by a paucity of methods to generate the densely functionalized multicyclic cores, which contain relatively large numbers of nitrogen atoms. In this work, we report a novel total synthesis of the marine alkaloid (+/-)-dibromoagelaspongin. Our key intermediate is a 2,5-diaminoisoimidazole accessed in one step from a guanylhydrazine and an amidoketone through a [3,3]-sigmatropic rearrangement-elimination sequence. The incorporation of the densely functionalized core in a single step bypassed the need for redox and protecting group manipulations, and the natural product was obtained in fewer than half the number of steps of the sole prior published route in excellent overall yield.

Automated summary

Marine alkaloids with a diaminoimidazole-derived core have fascinating chemical structures and have shown promising antimicrobial activity. However, the synthesis of these compounds is hindered by a lack of methods to generate the densely functionalized multicyclic cores that contain a relatively large number of nitrogen atoms. In this study, a new total synthesis of the marine alkaloid (+/-)-dibromoagelaspongin is reported. The key intermediate, a 2,5-diaminoisoimidazole, is accessed in one step, bypassing the need for redox and protecting group manipulations. The natural product is obtained in fewer steps than the previous route, and with excellent overall yield.