A Distinctive Structural Twist in the Aminoimidazole Alkaloids from a Calcareous Marine Sponge:  Isolation and Characterization of Leucosolenamines A and B

Abstract

Bioassay-guided fractionation of Papua New Guinea collections of Leucosolenia sp. resulted in the isolation of the novel compounds leucosolenamines A (5) and B (6) and the known compound thymidine (7). Compound 5 contains a 2-aminoimidazole core substituted at C-4 and C-5 by an N, N-dimethyl-5,6-diaminopyrimidine-2,4-dione and a benzyl group, respectively. Compound 6 retains the same core structure; however C-4 is substituted by a 5,6-diamino-1,3-dimethyl-4-(methylimino)-3,4-dihydropyrimidin-2(1H)-one moiety. This substitution pattern is unique and has never been observed in calcareous imidazole alkaloid chemistry. Leucosolenamine A (5) was mildly cytotoxic against the murine colon adenocarcinoma C-38 cell line.The sustained position of marine sponges as a source of structurally diverse and biologically active natural products was emphasized in a recent review article covering the 2003 literature. 1 Complex sponge natural products have also been the basis for the development of several clinical leads. 2 At the top of the list are natural products containing multiple chiral centers such as the bengamides, 3 fijianolides, 4 the halichondrin analogue E7389, 5 and the discodermolides 6 or sponge metabolites with exotic functionality, as in the psammaplins. 7 The research described in this paper began with the goal of adding additional unique structures to the rapidly growing list of sponge-derived alkaloids. In this regard, the Calcarea class of sponges is now recognized as a reliable source of richly bioactive metabolites possessing a 2-aminoimidazole 8 core that is often further substituted at the C-4 and C-5 positions. 9 The range of substitution patterns observed to date at these positions include (a) benzyl side chains, (b) oxo groups at C-4, and (c) annulation by five-or six-membered rings. Supporting Information Available:Compound isolation schemes, underwater and above water photographs of Leucosolenia sp., NMR spectra ( 1 H, 13 C NMR, gHMBC, gHMQC, DEPT) and MS spectra of 5, 6, and 7, ACD calculations and MOPAC-minimized structures of 5a and 5b, MS-MS data of 2, 5, and 8. This material is available free of charge via the Internet at http://pubs.acs.org. The structures of naamine C (1), 10 leucettamine B (2), 11 spirocalcaridine A (3), 8c and 2-amino-2-deoxykealiiquinone (4) 12 provide illustrations of these structural features. NIH Public AccessInvestigations to date of Calcarea sponges have been restricted to the genera Leucetta (syn. Pericharax) and Clathrina (both of the order Clathrinida, family Leucettidae). Yet, in view of the rich chemistry discovered, it is surprising that very little chemical work has been conducted on other members of this taxonomic class comprised of sponges in five orders spanning more than 75 genera. 13 The major impediment to further studies of this group is that they appear to be less abundant and poorly described in comparison to the class Demospongiae. During recent expeditions to Papua New Guinea (PNG), specimens of the genus Leucosolenia (order Leucosolenida, fam...

Ehrenasterol and biemnic acid; new bioactive compounds from the Red Sea sponge Biemna ehrenbergi

“…It is worthy to mention that hopanoid derivatives have been isolated mainly from bacterial sources in addition to sponges (Neunlist et al, 1988;Neunlist and Rohmer, 1985;Inatomi et al, 2000;Costantino et al, 2001). Similarly, after investigation of the different spectral data of compounds 7 and 8, they were identified as the known nucleosides thymidine and 2 0 -deoxyuridine respectively, which were previously isolated from different marine organisms (Zhou et al, 2005;Ralifo et al, 2007;Hammoda et al, 2007;Abou-Hussein et al, 2007;Deng et al, 1998).…”

“…In the course of our continuous effort to identify bioactive compounds from Red Sea marine sponges, we have studied the sponge Biemna ehrenbergi. This study resulted in the identification of two new compounds including one sterol, ehrenasterol (1), and an acetylenic acid, biemnic acid (2) together with the previously reported compounds; (22E)-ergosta-5,8,22-trien-7-one-3b-ol (3) (Luo et al, 2006), 32,35-anhydrobacteriohopanetetrol (4) (Bradley et al, 2010;Cooke et al, 2008;Costantino et al, 2001), (24R)-ergosta-6,22-diene-5,8-epidioxy-3-ol (5) (Xiaochun et al, 2008), melithasterol B (6) (Xiaochun et al, 2008), thymidine (7) and 2 0 -deoxyuridine (8) (Zhou et al, 2005;Ralifo et al, 2007;Hammoda et al, 2007;Abou-Hussein et al, 2007;Deng et al, 1998). The structures of the compounds were achieved based on different spectroscopic data including HRESIMS, 1D ( 1 H NMR and 13 C NMR) and 2D (COSY, HSQC, and HMBC) NMR spectroscopy.…”

Isolation of 2 new metabolites, JBIR-74 and JBIR-75, from the sponge-derived Aspergillus sp. fS14

“…The Calcarea class of sponges has been recognized as a reliable source of richly bioactive metabolites possessing a 2-aminoimidazole skeleton. [12][13][14] However, the isolation of fungi from calcareous marine sponges has not been reported. Therefore, we attempted to isolate marine fungi from an unidentified calcareous marine sponge and then searched for secondary metabolites in the cultures of the isolated strains.…”

In vitro and in vivo antineoplastic activity of a novel bromopyrrole and its potential mechanism of action

“…Alkaloids of marine origin are widely distributed in marine sponges with widespread biological activity (Faulkner, 2002). Over the last 30 years, about 140 bromopyrrole alkaloids with various structures have been isolated from marine sponges, and they possess dynamic biological activities, such as antifungal, antitumour and immunosuppressive activities (Ralifo et al. , 2007; Tsukamoto et al.…”