2-Aminoimidazole alkaloids

An Australian sponge Axinella sp. has afforded the novel axinellamines A-D (1310-1313), which exhibit activity against Helicobacter pylori (1301). The similar massadine (1314) from the Japanese sponge Stylissa aff. massa inhibits geranylger-anyltransferase type I and the fungus Candida albicans (1302). Like many of these 2-aminoimidazole alkaloids, 1310-1314 were isolated as acid salts trifluoroacetic acid salts in these cases. 

In a study of the synthesis of marine 2-aminoimidazole alkaloids, the aminal C-N bond of bicyclic 898 was cleaved regioselectively to form the allylic amine 899. Deuterium exchange results in H-1, H-2, and H-5, but not H-7 exchange, although the C(6)-C(7) double bond underwent isomerization 901. This is atributed to the assistance of the carbamoyl group that formed the oxazoline 900. Hydrolysis of the carbamate group of 899 under basic conditions affords either pyrrole 902 or pyridine 903 (Scheme 218) <2004OL3933>. 

The nudibranch Notodoris citrina, which feeds on the yellow sponge Leucetta chagosensis was found to concentrate substituted 2-aminoimidazole alkaloids including naamidine A [9 5],naamine A [9 6], isonaamidine [9 7] and isonaamine A [9 8] (79). 

Vergne, C., Boury-Esnault, N., Perez, T., Martin, M., Adeline, M., Dau, E. T. H., Al-Mourabit, A., (2006). Verpacamides A-D, a sequence of C11N5 diketopiperazines relating cyclo(Pro-Pro) to cyclo(Pro-Arg), from the marine sponge Axinella vaceleti Possible biogenetic precursors of pyrrole-2-aminoimidazole alkaloids. Org. Lett. 8, 2421-2424. 

Pyrrole 2-aminoimidazole alkaloids (PIAs) represent one of the most important groups of sponge secondary metabolites which show a large panel of biological activities [308]. Marine sponges, specifically the Agelasidae and Leucetta families, are the primary sources of structurally diverse secondary metabolites containing a 2-aminoimidazole functionality. Oroidin, isolated in 1971 by Forenza et al., was the first discovered member of this alkaloid family, and since then nearly 150 additional natural products have been isolated [309, 310]. 

Ando N, Terashima S (2010) A novel synthesis of the 2-amino-lH-imidazol-4-carbaldehyde derivatives and its application to the efficient synthesis of 2-aminoimidazole alkaloids, oroidin, hymenidin, dispacamide, monobromodispacamide, and ageladine A. Tetrahedron 66 6224-6237... 

Lastly, styhssazoles A-C are new complex pyrrole-2-aminoimidazole alkaloids (P-2-AI) that were isolated from Stylissa carteri collected in the Solomon Islands (Patel et al, 2010). These findings confirm the proposed universal biosynthetic pathway for all currently known dimeric P-2-AI compotmds (Al-Mourabit and Potier, 2001 Kock et al, 2007). 

S. C.J., and Van der Eycken, E.V. (2010) Concise and diversity-oriented route toward poly substituted 2-aminoimidazole alkaloids and their analogues. Angew. Chem. Int. Ed., 49, 9465-9468. 

Carmely, S., Ilan, M., and Kashman, Y. (1989) 2-Aminoimidazole alkaloids from the marine sponge Leucetta chagoensis. Tetrahedron, 45, 2193-2200. 

Structural Characterization of Donnazoies A andB, NovelPyrrole-Aminoimidazole Alkaloids from the Marine Sponge Axinella donnai... 

Munoz and coworkers [47] isolated and characterized two novel pyrrole— aminoimidazole alkaloids, donnazoies A and B (17 and 18, respectively) from the sponge A. donnai. Data were reported for 17 as the formate salt in d4-methanol and as the triflate salt in dy-DMF, with full assignments from a HMBC spectrum reported for the latter sample. Unfortu-... 

Mourabit AA, Potier P (2001) Sponge s Molecular Diversity Through the Ambivalent Reactivity of 2-Aminoimidazole A Universal Chemical Pathway to the Oroidin-Based Pyrrole-Imidazole Alkaloids and Their Palau amine Congeners. Eur J Org Chem 237... 

Assmann et al. described, in addition to known alkaloids, the isolation of the first pyrrole-imidazole alkaloid with a guanidine function instead of the aminoimidazole (127) [152] from the sponge Agdas wiedenmayeri, while its decarboxylated derivate laughine (128) was isolated from the sponge Eurypon laughlini [153],... 

Mourabit AA, Potier P. Sponge s molecular diversity through the ambivalent reactivity of 2-aminoimidazole a universal chemical pathway to the oroidin-based pyrrole-imidazole alkaloids and their palau amine congeners. Fur. J. Org. Chem. 2001 2 237-243. 

Fig. (9). Aminoimidazole and guanidine type of alkaloids from Axinella carteri.

A number of such 2-aminoimidazole-based alkaloids have been isolated and structures elucidated, including preclathridines, clathridines [4—8], naamidines, isonaamidines, naamines, isonaamines, and pyronaamidine (see Chart 1). 

Much like the structures of saxitoxin and tetrodotoxin, the family of pyr-role-aminoimidazole (PAI) alkaloids, including the axinellamines, massadines, and palau amine, have reinvigorated the field of organic synthesis to... 

Al-Mourabit A, Zancanella MA, Tilvic S, Romo D (2011) Biosynthesis, asymmetric synthesis, and pharmacology, including cellular targets, of the p5frrole-2-aminoimidazole marine alkaloids. Nat Prod Rep 28 1229-1260... 

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