Discorhabdin alkaloids

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. 

Yang A, Baker BJ, Grimwade J, Leonard A, McClintock JB (1995) Discorhabdin Alkaloids from the Antarctic Sponge Latrunculia apicalis. J Nat Prod 58 1596... 

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. 

Grkovic T, Ding Y, Li X-C, Webb VL, Ferreira D, Copp BR (2008) Enantiomeric discorhabdin alkaloids and establishment of their absolute configurations using theoretical calculations of electronic circular dichroism spectra. J Org Chem 73 9133-9136... 

Aubart KM, Heathcock CH (1999) A biomimetic approach to the discorhabdin alkaloids total syntheses of discorhabdins C and E and dethiadiscorhabdin D. J Org Chem 64 16-22... 

A/ illNoronono alkaloids Benzylisoquinoline alkaloids p-carbollno alkaloids Cyclopeptide alkaloids Dilerpene alkaloids DIscorhabdin alkaloids Ergot alkaloids Hasiibanano-lype alkaloids Imidazole alkaloids Indole alkaloids Indolo-diterpene alkaloids Indolocarbazole alkaloids Isoqninoline alkaloids Loline alkaloids... 

Discorhabdin alkaloids have the richest structure-diversity among the marine pyrroloiminoquinone alkaloids. Although many synthetic studies have been carried... 

For example, a variety of natural products bearing spirocyclic systems exist, and many of them are biosynthetically formed by oxidative spiroannulation processes. Hypervalent iodine(III) reagents are thus considered as one of the most effective oxidants for these oxidation processes. Several efficient methods for PIFA-induced spiroannulation reactions of phenols [48, 49] towards the total synthesis of discorhabdin alkaloids [50, 51] and their oxa-analogues have been published [52, 53], which were accomplished via hypervalent iodine oxidation of phenols or (9-trimethylsilylated phenol derivatives to the azacarbocyclic spirodienones as a key step (Scheme 8). 

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). 

Like the prianosins and the discorhabdins, the batzellines and isobatzellines are sulfides with a pyrroloquinone skeleton [22]. A deepwater Batzella sponge contained the alkaloids, batzellines A (457) and B (458), which possess methyl sulfide groups. The structure of... 

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... 

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... 

Harayama Y, Kita Y (2005) Pyrroloiminoquinone Alkaloids Discorhabdins and Makaluvamines. Curr Org Chem 9 1567... 

Tohma H, Harayama Y, Hashizume M, Iwata M, Egi M, Kita Y (2002) Synthetic Studies on the Sulfur-Cross-Linked Core of Antitumor Marine Alkaloid, Discorhabdins Total Synthesis of Discorhabdin A. Angew Chem hit Ed 41 348... 

Oxidative cyclizations of 3-(/ -azidoethyl)indoles with BTIB afford pyr-roloiminoquinones 15, compounds that appear as sub-structures in biologically active marine alkaloids such as the makaluvamines and discorhabdins (Scheme 22) [67- 69]. In fact, BTIB-mediated sulfide and azide cyclizations, and a-azido-nation of the cyclic sulfide with PhIO/TMSN3, were incorporated into the first total synthesis of ( )-makaluvamine F [68,69]. 

Several efficient methods for PIFA-induced spiroannulation reactions of sily-lated phenol derivatives [44] or phenols [45] toward total synthesis of dis-corhabdin alkaloids having potent cytotoxicities and unique structures have been developed by Kita and co-workers. Utilizing these methodologies, total syntheses of discorhabdin C (30) [106] and discorhabdin A (31) [107] have been accomplished (Scheme 20,21). 

Nucleophilic attack of the electron-rich aromatic ring 124 to the cationic complex 123, and intramolecular amination afforded the intermediate 125 for the synthesis of discorhabdin and prianosin alkaloids [29]. 

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. 

The pyrroloquinoline alkaloid family of bioactive marine natural products has been assembled by exploiting a biomimetic strategy. In the case of the iV-benzyl derivative of discorhabdin C (281a), for example, the cation 282 that is formed upon electrooxidation of dibromophenol 279 was intercepted intramolecularly to afford 281a in modest 19% yield [70]. Unfortunately, all attempts to remove the benzyl group failed. Consequently, the approach to the natural product was modified to affect debenzylation earlier in the scheme. Electrochemical oxidation of the free amine 280 did lead to discorhabdin C (281b), albeit in a low yield (24%). 

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. ... 

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