Prianosins-discorhabdins

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. 

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... 

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. 

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... 

Keywords Bispyrroloiminoquinone- Discorhabdin Isobatzelline Makaluvamine-Pyrroloiminoquinone alakloid Prianosin B... 

Our group accomplished the total syntheses of discorhabdin C in 1992 [38], makaluvamine F in 1999 [39, 40], and discorhabdin A in 2002 [41, 42]. We also accomplished the first total synthesis of prianosin B in 2009 [43]. We now report the progress towards the synthesis of pyrroloiminoquinone alkaloids, mainly since 2000 including our studies, in this chapter. 

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. 

Prianosin B is the oxidized discorhabdin A, whose C16-17 bond is double bond. We found that the detosylation and dehydrogenation reaction of the pyrroloiminoqumone unit proceeded using a catalytic amount of NaN3 in good yield. We then applied the reactions to the total synthesis of prianosin B (Scheme 33). Thus, the treatment of 98... 

Nishiyama S, Cheng JF, Tao XL, Yamamura S (1991) Synthetic studies on novel sulfur-containing alkaloids, prianosins and discorhahdins total synthesis of discorhabdin C. Tetrahedron Lett 32 4151-4154... 

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. 

Prianosin B is a C16-17 dehydro-derivative of discorhabdin A. Thus, treatment of intermediate 34 in the discorhabdin A synthetic pathway (Scheme 9.9) with NaNs brought about simultaneous detosylation and dehydrogenation to produce prianosin B in 48 % yield. (Scheme 9.10) [51]. 

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