| Research Abstract |
Tetracyclic eudistomin (1), Which were isolated out of the colonial tunicate Eudistomin olivaceum, possessed very potent antiviral and antitumor activities.
Upon oxidation of azetopyridoindoles (2, 3), which were synthesized from tryptamine via several steps, with MCPBA, oxazepinopyridoindoles (4, 5) were obtained by Meisenheimer rearrangement of the corresponding N-oxides. The framework of these oxazepines correspond to that of 12-carba-analog of eudistomin (1). Thus, synthesis of 12-carbaeudistomin analogs (6-9) is attractive from the point of the study of the structure-activity relationship.
Dihydro derivative (6,alpha-isomer) of 4 was hydrolyzed with AlBr_3-EtSH to the corresponding carboxylic acid, which could be converted to alpha-amino derivative (7) via Curtius decomposition. Similarly, beta-amino derivative (7) was synthesized from beta-isomer of ester (6). In order to obtain the unsubstituted derivatives (9) on indole nitrogen atom, the phenylsulfonyl group, which could be removed by reduction with Mg-MeOH, was suitable as a protective group. Thus, oxazepine (5) was converted to alpha-and beta-amino derivatives (9) according to the similar method for the preparation of N-methyl derivatives (7).
Antiviral activity of four compounds synthesized was evaluated. Among them, only beta-amino derivatives possessed activity. It is of interest that especially beta-amino derivative of 9, which is considered to be 12-carbaeudistomin, was the strongest.
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