ChemInform Abstract: 2-Aminoimidazoles from Leucetta Sponges: Synthesis and Biology of an Important Pharmacophore

This review will focus on the ability of the 2-aminoimidazole to occupy a unique subset of chemical space which makes it an ideal pharmacophore for the development of small molecule collections for discovery based research. These observations rely both on the use of 2-aminoimidazoles as building blocks in medicinal chemistry as well as the recent discovery of alkaloids from sponges of the genus Leucetta which exhibit a diverse range of biological activities around a relatively limited structural core. The preparation of these compounds will also be highlighted. In particular, marine natural products derived from sponges have provided valuable leads for therapeutic small molecules (3, 4). Surprisingly the large majority of these compounds have been isolated from organisms of the class Dermospongiae. In the mid 1980's chemists noted that the other major sponge class, Calcarea, had rarely been subject to chemical investigations. A flurry of efforts through the mid-1990's helped to establish biogenetic relationships among these sponges. Isolated to explore these inter- connections and not necessarily for specific biological responses the activities of these natural products have remained largely uncovered. Since these initial inves- tigations, an emerging structural class has recurrently been identified through bioassay guided isolation which contains the 2-aminoimidazole core. From the viewpoint of small molecule discovery this review will highlight alkaloids isolated from Leucetta sp. This small skeletal family has been shown to interrogate an incredibly diverse range of biological processes and thus represents an important discovery scaffold for both medicinal and discovery based research.