Prianosins

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... 

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... 

Zyzzya genus [58]. The structure of prianosin A (= discorhabdin A) (52), including its absolute configuration, was unequivocally defined by X-ray analysis [54], while those of discorhabdins B (54) and D (57) were based on spectral data. The previous structures proposed for prianosins C and D [55] were revised to 2-hydroxydiscorhabdin D (56) and discorhabdin D (57), respectively [59]. A plausible biosynthetic pathway for these compounds suggests the involvement of a-amino acids tyrosine (C-l-N-9) and tryptophan (C-10-C-21) [55]. 

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]. 

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 1987, Kobayashi et al. reported on the isolation of a novel alkaloid, prianosin A (481), from the Okinawan marine sponge Prianos melanos (204). The methanol-toluene extract of the green sponge, which was collected at a depth of 2 to 3 meters in the Motobu Peninsula of the Okinawa Island, was partitioned between toluene and water. The water layer was extracted with chloroform and extensive column chromatography afforded prianosin A (481) (0.02%, wet wt.). 

The structure elucidation of prianosin C (488) and prianosin D (484) were first carried out with their acetate forms because of their high polarity and instability in solution. Their structures were determined as C (491) and D (492), and the corresponding acetate derivatives as C (489) and D (490) using spectroscopic techniques, including H- C COSY, DEPT, HOHAHA, and HMBC. 

RsOH Prianosin C (2-tiydro)vdi8corhabdln D) R=H Prianosin D (Disooitiabdin D)... 

Prianosins B (487), C (488), and D (484) were found to be cytotoxic against murine lymphomas L1210 and L5178Y cells and human epidermoid carcinoma (KB) cells in vitro, with IC50 values of 2.0,1.8, and >5.0 fig/ml... 

Yamamura et al. developed an efficient route to the synthesis of the A, B, C, D, and E rings of the prianosins and discorhabdins, which led them successfully to synthesize discorhabdin C (Scheme 59) (210-212). Because their route involves the synthesis of the pyrroloquinoline skeleton of the pyrroloquinoline type alkaloids (213-217), they have also achieved the synthesis of batzelline C and isobatzelline C (213,214). Their synthesis involved first the construction of the C, D, and E rings as in 505, starting from 502, which was synthesized in three steps (212). Reaction of 502 with... 

Knolker et al. have developed a one-pot diastereoselective spiroannela-tion by electrophilic substitution of an aromatic system with an iron-complexed cation, which led to the construction of the A, B, C, and D rings of the prianosins and discorhabdins. This novel diastereoselective spiroannulation involved the reaction between the tricarbonyliron-complexed cation 520, which was prepared in six steps (2/9), and an arylam-ine, the 6-aminoindoline (521), to construct A, B, C, and D rings (512) (Scheme 61) (220). The stereochemistry of the product was determined by X-ray crystallographic analysis the stereodirecting effect of Fe(CO)3 was indicated to be anti to the aryl ring (2/9). 

A synthetic methodology has been under investigation for the synthesis of discorhabdins and prianosins by Confalone et al. using intramolecular... 

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