Complex imidazole alkaloids

In a series of three papers published in 1998, Schmitz and co-workers explored the chemical constituents of Micronesian marine sponges using 3 mm NMR probe technology. In the first of these papers, several imidazole alkaloids and their Zn + 2 complexes were isolated and characterized from the sponge Leucetta cf. chagosensis96... 

The first examples of tetrameric pyrrole imidazole alkaloids, stylissadine A (100) and B, were isolated from the Caribbean sponge Stylissa carihica in 2006 [128]. They possess a symmetric dimeric stmcture derived from condensation of two massadine units, and differ in the configuration at the center C-2. Stylissadines represent the largest pyrrole-imidazole alkaloids isolated so far, and, with their 16 stereogenic centers, they are the most complex stmctures known within the oroidin alkaloid family. 

In a very interesting report from 2001, Ciminiello and coworkers [73] reported the isolation and structural characterization of the complex bromotyrosine-derived imidazole alkaloid archerine (38) that was isolated from the Caribbean marine... 

The pyrrole-imidazole alkaloids, mainly isolated from various species of the Agelasidae, Axinellidae, Dyctionellidae, and Hymeniacidonidae sponge famihes, contain characteristic pyrrole-2-carboxamide and 2-aminoimidazoline moieties or derivatives thereof. Their architectural complexity ranges from simple, achiral, monomeric oroidin to the 16-stereocenter-containing tetrameric stylissadines A and B (Fig. 9.4). Because many reviews have appeared describing these alkaloids [52-56], we provide only a short discussion of some biosynthetically and synthetically pertinent information. 

The structures of two tetrameiic alkaloids, stylissadine A and B that are ether-linked dimers of massadine, are shown in Fig. 9.4. Although these substances are antagonists of the P2X7 receptor involved in inflammatoiy diseases, no reports have appeared describing their S3mtheses, perhaps because they have the most complex structures of p3Trole-imidazole alkaloids discovered so far. 

Fu, X., Schmitz, F.J., Tanner, R.S., and Kelly-Borges, M. (1998) New imidazole alkaloids and zinc complexes from the Micronesian sponge Leucettad. chagoensis. ]. Nat. Prod., 61, 384-386. 

Imidazole Alkaloids and Zinc Complexes Isolated from the Genera Leucetta, Leucosolenia, and Clathrina... 

In 1989, clathridine and its zinc complex were isolated from Clathrina clathrus, and the structure of the zinc complex in the solid state was obtained by X-ray diffraction (Ciminiello et al., 1989,1990a). Subsequently, other chiral zinc complexes were isolated with imidazole alkaloids from sponges of the genus Leucetta (Alvi et al., 1993 Mancini et al., 1995 Fu et al., 1998a). The roles of such complexes in sponges are still unknown. 

Among the more complex structures, carteramine A and stylissadines A and B are respectively dimers (C22N10) and tetramers (C44N20) of C11N5 pyrrole-imidazole alkaloids. Isolated from the species Stylissa carteri harvested in Japan, carteramine A is an inhibitor of neutrophil chemotaxis (IC50 5 pM), and may lead to a new generation of anti-... 

Baran, P.S., O Malley, D.P., and Zografos, A.L. (2004) Natural product synthesis sceptrin as a potential biosynthetic precursor to complex pyrrole-imidazole alkaloids the total synthesis of ageliferin. Angeiv, Chem, Int. Ed., 43, 2674-2677. 

Bromination of the pyrrole 4-position or of the imidazole part has never been observed. A great molecular diversity is observed in this group of alkaloids extremely varied chemical architectures are reported, ranging from linear oroidin-like monomers to complex polyciclic and tetrameric molecules. In this chapter illustrative structures of this alkaloids family are reported, divided into the following groups ... 

Clathridine, an unusual alkaloid derived from imidazole and guanidine, was isolated in 1989, in the form of a 2 1 complex with a zinc atom, in the sponge Clathrina clathms. Since 1990, some other complexes of zinc have been isolated from calcareous sponges, such as the complex containing isonaamidine C (Alvi et al, 1993 Mancini et al, 1995 Fu et al, 1998). For additional information, see Chapter 19. 

The presence of alkaloids containing one or two imidazole nuclei is the main feature of the genus Leucetta, and several of these compounds exist in the form of a complex with zinc ion (see Chapter 3). The main results on the genus Leucetta are summarized in Table 19.3. 

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