Discorhabdin isolation

The biosynthesis of the halichondrins, a family of compounds isolated from Lissodendoryx sp., was found to be associated with Percoll-enriched fractions of choanocytes and spherulous cells.109 The discorhabdins, isolated from Latrunculia brevis, were also observed to be associated with sponge cells using similar techniques. 

Oxidation of l-amino-4-methoxybenzenes with CAN is expected to afford p-iminoqninones. Thns, batzellines, makalnvamines and discorhabdins, isolated from marine organisms, possess a pyrroloiminoqninone moiety and can be synthesized by CAN-mediated oxidation of the corresponding 4-amino-7-methoxyindole derivative. 

A family of alkaloids characterized by a pyrroloquinone skeleton has been isolated in recent years from several sponges. Included in this family are the batzellines, isobatzellines, damirones, makaluvamines, discorhabdins, prianosins and wayakin. These alkaloids have shown a... 

Discorhabdin alkaloids, Fig. (31), in contrast, are of high cytotoxicity, but they exhibit no inhibition of topoisomerase II. They were isolated from the Anthartic sponge Latrunculia apicalis [238], and more recently from a deep-water marine sponge of the genus Batzella sp. [239], The new discorhabdin derivative isolated from this sponge showed in vitro cytotoxicity against tumor cell lines. 

Discorhabdins A (8), B (9) and C (10) have been isolated from several sponge species of the genus Latrunculia from New Zealand. They are powerful cytotoxins with IC50 values against the murine leukemia P-388 cell line in the range 0.03 - 0.01 pg/ml. Discorhabdin A has also been isolated from a Japanese sponge of the genus Prianos [29]. 

The sulfide marine metabolites having a pyrroloquinoline skeleton can be divided into three groups the batzellines-isobatzellines, the prianosins-discorhabdins, and the makaluvamines. All of these types of compounds have been isolated from sponges. 

These complex sulfide-containing pyrroloiminoquinone alkaloids consist of the prianosins A-D (52, 53, 56, 57), isolated from the Okinawan Prianos melanos [54, 55], the discorhabdins A and B (52, 54), obtained from three different species of the New Zealand Latrunculia [56], discorhabdin D (57) from Latrunculia brevis and Prianos sp. [57], and discorhabdin Q (55), from Latrunculia purpurea, and several species of... 

Discorhabdin and related pigments have been isolated from temperate and tropical sponges of the genera Latrunculia, Prianos, Zyzzya, and Batzella 94 discorhabdin C (Structure 7.11)95 and G (Structure 7.12)38 were recently found in Latrunculia apicalis collected from McMurdo Sound.96 Discorhabdins often bear significant cytotoxicity. Discorhabdin C is perhaps the strongest sea star deterrent studied to date and displays broad spectrum antibiotic activity toward sympatric bacteria.38 96... 

Alkaloids related to pyridoacridines are known also from sponges and tunicates. Discorhabdin C (79), which is the first marine pyrroloquinoline alkaloid, was isolated from the sponge Latmnculia cf. bocagei. More than 20 alkaloids of this class are known at moment (30). Additional examples of this family are batzelline A (80) from a deep-sea sponge of the genus Batzella and wakayin (81) from an ascidian Clavelina sp. 

Of physiologically active substances isolated from marine sources, the pyrroloimino-quinone alkaloids family exhibits antitumor activities derived from the unique highly-fused structure. The first synthesis of discorhabdin C (127) was performed by means of an electrochemical method as a key step . The key substrate 128, efficiently prepared starting from 4,4-dimethoxy-5-nitrobenzaldehyde, was submitted to constant current electrolysis (3 mA 4-1.2-1.8 V vi. SCE) in anhydrous MeCN to give rise to discorhabdin C in 24% yield, together with a minor compound 129 (6%) (Scheme 24). After a while, discohabdin C was also synthesized by using PhI(OCOCF3)2-promoted oxidation as a key step. ... 

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>. 

The alkaloids containing the pyrroloquinolinequinoneimine subunit isolated so far are called discorhabdins (481-486) and prianosins (481, 484, 487,488). They are very similar natural products that are examined together. 

Some of the compounds that were isolated and named by independent groups were later noticed to be actually the same compounds. Thus, discor-habdin A (481) and discorhabdin D (484) are identical with prianosin A and prianosin D, respectively. 

Although their isolation, characterization, and biological activities are reviewed individually, synthetic studies toward discorhabdin and prianosin are examined under the same topic because each synthetic study is closely related to both groups of alkaloids. 

In 1986, Munro et al. reported the isolation of discorhabdin C (483) from a red-brown marine sponge of the genus Latrunculia du Bocage (195,196),... 

Almost at the same time, Blunt et al. 200) reported on the isolation and structure elucidation of discorhabdin D, which corresponds to the dehydro form of the phenol moiety of 492. In 1990, the same group reported 2-... 

The bioactive pyirolo[4,3,2-de]quinoline alkaloids B. are isolated from the Caribbean sponge Batzella sp., living at a depth of about 120 m. B. AC,2H,, C1N2C>2S, Mr 282.74, black prisms, mp. 205 °C isobatzellineA C12H12CIN3OS, Mr 281.77, brown solid, active against P388 leukemia cells and Candida albicans. They may be biosynthetic precursors of the discorhabdins. 

A similar intramolecular cyclization of 3-(azidoethyl)indole derivatives 309 provides an efficient route to the pyrroloiminoquinone system 310 (Scheme 3.127), which is an essential component of several recently isolated marine alkaloids such as makaluvamines, isobatzelline C and discorhabdins, which possess potent biological activities [372]. 

S, T, and U [29] possess methyl sulfide moieties, discorhabdin W [30] is a dimeric structure linked by a disulfide bond, while other members of this series do not contain sulfur. Furthermore, discorhabdins F [31], Q, S, and T and prianosin B contain a 16,17-dehydropyrroloiminoquinone moiety. The enantiomeric pairs of discorhabdins B, G /I, L, and W were also isolated from Latrunculia species sponges [32]. A study focusing on the elucidation of the absolute stereochemistry of several discorhabdins was reported by Copp et al. [33]. 

Sequences for the synthesis of the more complex discorhabdins, discorhabdin A and prianosin B, have been developed only in our laboratoiy. Discorhabdin A, which has a unique sulfur-containing fused ring structure, incorporating azacarbocyclic spirocyclohexanone and pyrroloiminoquinone systems, displays the most powerful cytotoxic activity among isolated members of the discorhabdin family. 

An interesting case of chemotypy has been described for New Zealand Latrunculia spp. sponges collected in the remote SW comer of the country (Doubtful and Milford Sounds) yield discorhabdin alkaloids that are enantiomers of those isolated from sponges collected in other regions of New Zealand (Grkovic et al, 2010). 

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