A New Concise Synthesis of Arcyriacyanin A and Its Unique Inhibitory Activity against a Panel of Human Cancer Cell Line.

Abstract

The nucleophilic addition reaction of N-tosyl-4-oxo-4,5,6,7-tetrahydroindole (12) with the lithium salt of 1-methoxyindole (5), followed by dehydration with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) gave the derivative of 2,4'-bi-1H-indole (9) which provides a new concise synthetic method of an indole pigment of the slime mould, arcyriacyanin A. The compound was first demonstrated here to have unique inhibitory activity to a panel of human cancer cell lines and to inhibit protein kinase C and protein tyrosine kinase.

New Synthetic Route to Granulatimide and Its Structural Analogues.

“…Subsequent deprotection of the 1-methoxy group in 14 and 25 was readily achieved with Mg-methanol 13) in tetrahydrofuran (THF) to give, in 75 and 93% yields, 4-(1H-indol-2-yl)-1-(methoxymethyl)-1H-imidazole (15) and 4-(1H-indol-2-yl)-1-methyl-1H-imidazole (26), a key intermediate for the syntheses of granulatimide and its analogues.…”

“…The next stage in the syntheses of 7 and its analogues was carried out by the reaction of the maleimide 17 (or 18) with the Grignard reagent 16 (or 27) prepared from the coupling product 15 (or 26) according to our previous synthesis 12,13) with some modifications. The reaction of 15 (or 26) with ethylmagnesium bromide in absolute THF gave the MgBr salt 16 (or 27).…”

“…6,10,11) Recently, we reported the synthesis and protein kinase C inhibitory activity of arcyriacyanin A (6), 12,13) an unsymmetrically substituted green-blue indole pigment of the slime mould Arcyria obvelata ONSBERG (Arcyria nutans GREV. ).…”

“…Our strategy for the synthesis of granulatimide (7) and its analogues is illustrated in Chart 2. The application of our method for the synthesis of arcyriacyanin A 13) should allow the synthesis of 7 by reaction of the bromomagnesium salt of the indole-imidazole 10 with 3,4-dibromomaleimide.…”

Total Synthesis of the Slime Mold Alkaloids Arcyroxocin A and B

“…2 Thus, the tiny red sporangia of Arcyria species contain condensed alkaloids of the arcyriaflavin (2), 3 arcyriacyanin (3), 4 and arcyroxocin types 4 ( Figure 1), 2a,b,5,6 which are biogenetically related to the more simple arcyriarubins (1). 3 Several of these compounds are inhibitors of protein kinases, 7 and the arcyroxocins A (4a) and B (4b) exhibit cytotoxicity against Jurkat cells. 6 Since these alkaloids can only be obtained in small amounts from the natural sources, their synthesis is of importance for pharmacological studies.…”