Oroidin dimer

Tsukamoto S, Kato H, Hirota H, Fusetani N (1996) Mauritiamine, a New Antifouling Oroidin Dimer from the Marine Sponge Agelas mauritiana. J Nat Prod 59 501... 

Tsukamoto, S., Kato, H., Hirota, H., and Fusetani, N., Mauritiamine, a new antifouling oroidin dimer from the marine sponge Agelas mauritiana, J. Nat. Prod., 59, 501, 1996. 

Sclerosponges such as A. willeyana have been difficult to classify. Ho vever, the discovery of metabolites of the oroidin class lend support to the assignment of A. wilhyana to the order Agelasida. Bioassay-guided fractionation of the methanol extract of Agdas mauritiana led to the isolation of a new antifouling oroidin dimer named mauritiamine (8S) [122]. Its synthesis has been reported [123]. 

Vhh conplings together with chemical shifts have been calcnlated by Chini et al for kedarcidin chromofore and palau amine in the attempt to establish the correct configuration of these two compoimds prior to their total synthesis. Kedarcidin chromofore is a compoimd that belongs to the enediyne family of antitumor antibiotics, whereas palau amine is an oroidin dimer, belonging to the class of pyrrole-imidazole alkaloid family isolated from the sponge Stylotella aurantiwn. Populations of conformers in three cinchona alkaloid O-ethers at ambient and low temperatnres have been estimated by Bnsygin et al ... 

Scheme 7.40 Stereoselective synthesis of the cyclohexenyl core of oroidin dimers via a radical polycyclization.

Tan, X., Chen, C. (2006). Regiocontrol in Mn -mediated oxidative heterobicycfizations access to the core skeletons of oroidin dimers. Angewandte Chemie International Edition, 45, 4345-4348. 

Mauritiamine, a new antifouling oroidin dimer from the marine... 

Sivappa, R., Mukherjee, S., Rasika Dias, H.V., and Lovely, C.J. (2009) Studies toward the total synthesis of the oroidin dimers. Org. Biomd. Chem., 7, 3215-3218. 

Oroidine (138) and its dimer mauritiamine (139) from the sponge Agelas mauritiana inhibit larval metamorphosis at ED50 values of 19 and 15 (jg/ml, whereas 4,5-dibromopyrrole-2-carbamide promotes larval metamorphosis of the ascidian Ciona savignyi at a concentration of 2.5 (jg/ml [109]. 

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. 

The excellent reviews of Berlinck [1-5] have surveyed a great number of guanidine-type natural products. In addition, some guanidine-derived marine alkaloids have been reviewed by Kobayashi and Ishibashi [6,7]. Also, a recent book gave accounts of marine alkaloids including the phakellins, palau amines and oroidin-like dimers derived from bromopyrroles and polyketide-derived polycyclic guanidine alkaloids [8]. 

Figure 9. Oroidin-like dimers sceptrin (63) and its analogues 64-69.

Figure 10. Oroidin-like dimers konbu acidin A (70), axinellamines A-D (71-74), and massadine (75).

In Fig. 9.7 are displayed acyclic and cyclic dimeric members of the pyrrole-imidazole family. Nagelamide D, from Okinawan marine sponges of the genus Agelas, is a dimer comprised of oroidin monomer units connected between the C-10 and C-15 positions [80]. However, the assigned structure of this substance is questionable (see below). Sceptrin, isolated in 1981 by Faulkner and Clardy from Agelas sceptrum, is the first reported symmetric dimer comprised of hymenidin subunits [81]. 

Although the number of studies using (radio) labeled substrates in an attempt to confirm the generation of these PIAs in nature is limited, numerous biosynthetic hypotheses occupy the chemical/synthetic literature [34, 35]. These proposals represent all levels of the complexity spectrum for this family, from simple cyclic compounds derived from an oroidin monomer to those that result from dimerization of oroidin and further cyclizations. To prevent this chapter from occupying the whole book, only two examples will be presented in this subsection to serve as a general overview. 

The ability of the 2-aminoimidazole 36/37 to tautomerize allows it to incorporate both electrophilic and nucleophilic sites into the molecule simultaneously (Fig. 13.4). This concept is further emphasized when considering the vinylogous compound 38/39 (26), which is thought to make up the basic building block of the PIAs (oroidin). This ambiphiUc reactivity allows for the vast number of speculative cyclization and dimerization pathways. 

Home was able to provide support for the biosynthetic hypothesis that mauritiamine (197) results from dimerization of an oroidin-like species. Upon examination of the natural product stmcture, it appears to be the union of oroidin (25) and dispacamide (196) (Scheme 13.34). Home was able to dimerize vinyl aminoimidazole 26 under oxidative conditions to provide the core of mauritiamine (199) [130]. After installation of the dibromopyrroles via acylation, the natural product was realized in six steps from ornithine methyl ester (198), without the need for PGs. 

Oroidin and its derivatives may also read with themselves by oxidative coupling, giving dimers whose typical example is mauritiamine, isolated in 1996. This particular readivity of oroidin is due to the large number of tautomeric forms of the vinylog moiety of 2-amino-imidazole, the main effect of which is that the carbon 5 on the imidazole can become either an electrophilic or a nucleophilic site (Al Mourabit and Potier, 2001). The main tautomeric forms are shown in Figure 19.48. 

The coupling of the two tautomeric forms B and C of oroidin led to mauritiamine (Tsukamoto et al., 1996b), but there are other types of dimer, such as sceptrin and ageliferin, which may derive from a cycloaddition (2 + 2) or (4 + 2). Some of these dimers are presented below, illustrating the various possibilities of coupling between two oroidins or two analogs of oroidin. 

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