Arcyriarubin

In 2003, Ishibasi et al. reported the isolation of a further, biogenetically closely related, bisindolylmaleimide, dihydroarcyriarubin C (353), along with the previously known, arcyriarubin C (351) (Scheme 2.90) and arcyriaflavin C (347) (see Scheme... 

The structure, and the trans-relative stereochemistry, of dihydroarcyriarubin B (352) was confirmed by comparison of the product obtained from arcyriarubin B (350) by palladium-catalyzed hydrogen transfer from cyclohexene in boiling xylene. Under these conditions, only the thermodynamically more stable trans-diastereomer was formed. Based on these data, and the spectroscopic comparison with the hydrogenation product of arcyriarubin B (350), the structure 352 was assigned to dihydroarcyriarubin B (252) (Scheme 2.90). 

The H- and C-NMR spectra of dihydroarcyriarubin C (353) were very similar to those of arcyriarubin C (351), except for the presence of one sp methine proton at 6 4.44, which was assignable to the C-8 proton. The HMBC spectrum showed a cross peak from H-8 to C-8 (5c 48.2), and this HMBC correlation may be assigned to H-8 to C-8 (or H-8 to C-8), indicating the symmetrical structure of this alkaloid. This structure was further supported by its H- H COSY and HMQC spectra (334). Comparison of the H-NMR spectral data of synthetic cis- and frans-dihydroarcyr-iarubin A (339) indicated the frans-relative stereochemistry for the natural dihydroarcyriarubin C (353). Based on these spectral data, and comparison with arcyriarubin C (351), as well as with synthetic fraMS-dihydroarcyriarubin A, the structure 353 was assigned to dihydroarcyriarubin C (334,339) (Scheme 2.90). 

The UV spectrum [2max 256 (sh), 336, 433, and 634 nm] of arcyriaverdin C (355) indicated the presence of a bisindolylmaleimide framework with an extended conjugation (252). The structure of arcyriaverdin C (355) was confirmed by chemical correlation of arcyriaverdin C (355) with arcyriarubin C (351) (see Scheme 2.90) by oxidation of the latter with lead tetraacetate in chloroform. Based on these data, and spectroscopic comparison with the oxidation product of arcyriarubin C (351), the structure 355 was assigned to arcyriaverdin C (252) (Scheme 2.91). 

Hill et al. reported an efficient short synthesis of staurosporinone (293) using a palladium-mediated oxidative cyclization of the bisindolylmaleimide arcyriarubin A (349) as the key step (766). The key intermediate, arcyriarubin A (349), was prepared... 

Faul et al. reported an improved synthesis of arcyriarubin A (349) by reaction of indolylmagnesium bromide (1358) with dichloromaleimide (1366). Following Hill s route, 349 was transformed to staurosporinone (293) in three steps and 47% overall yield (see Scheme 5.225). This approach provides, so far, the shortest access to staurosporinone (293) with the best overall yield (771) (Scheme 5.228). 

Uang et al. reported a synthesis of staurosporinone (293) starting from arcyriarubin A (349). Oxidative photocyclization of bisindolylmaleimide 349 in the presence of a catalytic amount of iodine in THF/acetonitrile led to arcyriaflavin A (345) in 85% yield. Finally, using modified Clemmensen reduction conditions, arcyriaflavin A (345) was transformed to staurosporinone (293) in 68% yield (795) (Scheme 5.254). 

Fruit bodies of wild myxomycetes often have bright colors. In 1980 Steglich et al. isolated red and yellow pigments from methanol extracts of 2 g of the red fruit bodies of Arcyria denudata [7], Structure of these pigments were elucidated by spectral data as a series of bisindole maleimides, and they were named arcyriarubin B (1), C (2), arcyriaflavin B (3), C (4), and arcyrioxepin A (5). 1, 2, and 5 were red... 

The structures of these bisindole maleimides were confirmed by synthesis. The reaction of indolyl magnesium bromide (10) with 2,3-dibromo-A -methylmaleimide (11) in toluene led to bisindolylmaleimide (12), which was converted into arcyriarubin A (6) through alkaline hydrolysis followed by heating with ammonium acetate (Scheme 1). The reaction of 10 and 11 in THF yielded monosubstitution product (13) which after protection of the indole NH group with the Boc residue was used to prepare unsymmetrically substituted bisindolylmaleimide, arcyriarubin B (1) [8]. 

Steglich et al. also studied the constituents of the fruit bodies of Lycogala epidendrum [17] and isolated not only lycogarubins A-C (31-33) but also lycogalic acid A (35) [18], staurosporinone (36) [19], and arcyriarubin A (6) and arcyriaflavin A (7) previously isolated from Arcyria denudata. 

Dihydroarcyriarubin C (104), a new bisindole alkaloid, has been isolated from fruit bodies of a myxomycete Arcyria ferruginea, which was collected at Hao, Yasu-cho, Kochi Prefecture, together with two known bisindoles, arcyriarubin C (2) and arcyriaflavin C (4), and the structure of 104 was elucidated by spectral data. Arcyriaflavin C (4) was also obtained, together with arcyriaflavin B (3), from fruit bodies of Tub if era casparyi, which ( 16839) was collected at Mt. Miune, Monobe-mura, Kochi Prefecture, in November 1997. Arcyriaflavin C (4) was revealed to exhibit cell cycle inhibition activity on HeLa cells on the basis of flow cytometry studies. Fruit bodies of Fuligo Candida, which ( 23446) was collected at Motoyama-cho, Kochi Prefecture, in August 2002, were revealed to contain a relatively high quantity of cycloanthranilylproline (105). 

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