Discorhabdin biological activity

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]. 

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>. 

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. 

Although discorhabdins E (485) and F (486) have been reported, it appears that no further structural data are available in the literature apart from their biological activities, which are mentioned in the biological activity section. 

Among these alkaloid metabolites, the alkaloids containing the pyrroloimino-quinone 4 core skeletons comprise about 60 metabolites including makaluvamines, isobatzellines, discorhabdins, tsitsikammamines, and wakayin. There are several reviews of the structures, biological activities, and synthesis of the pyrroloimino-quinone alkaloids and their analogs [6-9]. 

Among the makaluvamines, makaluvamine F exhibits the most potent biological activity (e.g., cytotoxicity towards the human colon tumor cell line HCT-116 (IC50 = 0.17 mM) and inhibition of topoisomerase II). It has a labile N, S-acetal moiety for oxidation, etc. Synthetic efforts by several groups then resulted in only diverse preparations of the pyrroloiminoquinone unit. For the synthesis of more complex pyrroloiminoquinone alkaloids such as makaluvamine F and discorhabdin A (Fig. 6), we intended to develop several mild reactions. 

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]. 

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