Pyrroloiminoquinones, marine

Kraus has reported the synthesis of a tricyclic indole related to the pyrroloiminoquinone marine natural products (Scheme 10.9), in which an intramolecular SNAr and the reductive cyclization of a nitro aldehyde are involved as key steps.94 Related target compounds have been prepared by Joule and coworkers via a similar strategy.95... 

Moro-Oka, Y., Fukuda, T., Iwao, M. The first total synthesis of veiutamine, a new type of pyrroloiminoquinone marine alkaloid. Tetrahedron Lett. 1999, 40, 1713-1716. 

The isolation, biological activity, biosynthetic studies, and s)mtheses of the pyrroloiminoquinone marine natural products 81 have been reviewed <05NPR62>. Total syntheses directed at members of this class of compounds, specifically the discorhabdins and makaluvamines, were the subject of a separate review <05COC1567>. 

Kita Y, Egi M, Tohma (1999) Total synthesis of sulfur-containing pyrroloiminoquinone marine product, ( )-makaluvamine F using hypervalent iodine(III)-induced reactions. Chem Conunun 143-144... 

Wao M, Motoi O, Fukuda T, Ishibashi F (1998) New synthetic approach to pyrroloiminoquinone marine alkaloids. Total synthesis of makaluvamines A, D, I, and K. Tetrahedron 54 8999-9010... 

LaBarbera DV, Skibo EB (2005) Synthesis of imidazo[l,5,4-de]quinoxalin-9-ones, benzimidazole analogues of pyrroloiminoquinone marine natural products. Bioorg Med Chem 13 387-395... 

Hoang H, LaBarbera DV, Mohammed KA, Ireland CM, Skibo EB (2007) Synthesis and biological evaluation of imidazoquinoxalinones, imidazole analogues of pyrroloiminoquinone marine natural products. J Med Chem 50 4561 571... 

The oxidation of phenol ethers 311 bearing an alkyl sulfide side chain followed by treatment with aqueous methylamine selectively affords various dihydrobenzothiophenes 312 (Scheme 3.128) without yielding any sulfoxides as by-products [372]. This procedure has been applied in the total synthesis of the potent cytotoxic makaluvamine F, a sulfur-containing pyrroloiminoquinone marine product [373]. 

The first total synthesis of the potent cytotoxic marine natural product makaluvamine F (5) involved the preparation of 2,3-dihydrobenzothiophene 2 <99CC143>. Debenzylation and subsequent acid-catalyzed cyclization of thioether 1 gave 2 which was converted in four steps to 2-azido-2,3-dihydrobenzothiophene 3 using a combination of Phl=0 and McjSiNj for installation of the azide. Reduction of the azide followed by coupling the resultant amine with pyrroloiminoquinone 4 then gave makaluvamine F (5). 

Antunes EM, Copp BR, Davies-Coleman MT, Samaai T (2005) Pyrroloiminoquinone and Related Metabolites from Marine Sponges. Nat Prod Rep 22 62... 

Kita and co-workers have developed a concise and high-yielding procedure for preparing the pyrroloiminoquinone derivatives (158), which are key precursors of antitumor marine alkaloids, makaluvamine D (54), I (55), and M (56), from the phenol ether derivatives (157) bearing an alkylazido side chain using PIFA-TMSOTf [122] (Scheme 30). 

Makaluvamines (pyrroloiminoquinones) 51 (Fig. 4) isolated from a Fijian sponge in the early 1990s display in vitro cytotoxicity against human colon tumor cell Unes and also inhibit human topoisomerase II in vitro. The benzimidazole analog of this indole-based marine natural product, imidazo-quinoxaUnone 52, has been synthesized starting fromp-methoxydiacetanilide (Scheme 12) [51]. Treatment of the dinitration product 54 of p-methoxy-... 

Abstract Recent reports on the s) thetic studies of marine pyrroloiminoquinone alakloids and their analogs are reviewed. 

The representative makaluvamine alkaloids having the pyrroloiminoquinone skeleton are shown in Fig. 1. They were isolated from marine sponges collected in Fiji, Micronesia, Australia s Great Barrier Reef, Indonesia, the Philippines, and the Vanuatu area [10-15]. The stereogenic center of makaluvamine F has not been determined. V-l-p-D-Ribofuranosylmakaluvamine I, which has a sugar moiety, was also isolated from a South African sponge [16]. 

Figure 3 shows the alkaloids with the pyrrolo[4,3,2-de]pyrrolo[2,3-/t]quinoline skeleton, i.e., wakayin and tsitsikammamines. Wakayin was isolated from a Fijian ascidian and is the first pyrroloiminoquinone alkaloid not isolated from a marine sponge [19]. Tsitsikammamines A and B were isolated from a South African latrunculid sponge Latrunculiidae in 1996 [20]. They are reported to exhibit a cytotoxicity and topoisomerase I inhibition. Furthermore, reinvestigation of the extracts of the same sponge led to isolation of minor pyrroloiminoquinone... 

Discorhabdin alkaloids have the richest structure-diversity among the marine pyrroloiminoquinone alkaloids, and new discorhabdins are still being discovered. Although many synthetic studies have been carried out, only a few total syntheses of the natural discorhabdins have been reported. The total synthesis of discorhabdin C was accomplished by our group and Yamamura s group at almost the same time, and later by the Heathcock group. Heathcock et al. also synthesized discorhabdin E at the same time. Those discorhabdins are rather simple. The more complex discorhabdins, discorhabdin A and prianosin B, were synthesized only by us. 

Delfoune E (2008) Analogues of marine pyrroloiminoquinone alkaloids synthesis and antitumor properties. Anticancer Agents Med Chem 8 910-916... 

Izawa T, Nishiyama S, Yamamura S (1994) Total syntheses of makaluvamines A, B, C, D and E, cytotoxic pyrroloiminoquinone alkaloids isolated from marine sponge bearing inhibitory activities against topoisomerase II. Tetrahedron 50 13593-13600... 

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