Synthesis of 2-Aminoimidazole-Based Alkaloids

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DESCRIPTION (provided by applicant): The plan of this investigation is twofold in nature. The overall objective is to develop concise and efficient syntheses of synthetically and technically challenging 2-aminoimidazole based sponge alkaloids known as the oroidin alkaloids. In particular, we plan to synthesize sceptrin (4), dibromoagelaspongin (6), ageliferin (7), palau'amine (9), agelastatin D (12), and axinellamine (14). Collectively, these and other structurally related metabolites possess a myriad of potent biological effects. An important goal within this research endeavor is the development and validation of a unifying chemical approach to this structurally novel class of natural products. The proposed methods and routes are essentially devoid of protecting groups and are guided by biogenetic considerations. The synthetic plan calls for methods development for transforming 2- aminoimidazoles into key intermediates for the synthesis of the naturally occurring compounds. The preparation of these intermediates and the facility of the ensuing molecular rearrangements would tend to support or disclaim the biogenetic hypothesis. Versatile and efficient syntheses of these metabolites would provide access to structurally modified or specifically labeled substrates for biomedical research. In addition, the methods developed in this area will be applied to synthesis of the red-tide toxins, saxitoxin, gonyautoxin I and gonyautoxin IV.