Collect. Czech. Chem. Commun. 1999, 64, 348-362

Synthesis of Some Analogs of Indole Phytoalexins Brassinin and Methoxybrassenin B and Their Positional Isomers

Peter Kutschya,*, Milan Dzurillaa, Mitsuo Takasugib and Adriana Sabováa

a Department of Organic Chemistry, Faculty of Natural Sciences, P. J. Šafárik University, Moyzesova 11, 041 67 Košice, Slovak Republic
b Division of Material Science, Graduate School of Environmental Earth Science, Hokkaido University, Sapporo 060-0810, Japan


Treatment of indole-3-carboxylic acid with phosphorus trichloride and subsequent reaction of the obtained acid chloride with potassium thiocyanate afforded indol-3-ylcarbonyl isothiocyanate (13). Its treatment with sodium hydrogensulfide in the presence of methyl iodide lead to the corresponding methyl dithiocarbamate, an oxo derivative of brassinin (oxobrassinin, 14), which by methylation with methyl iodide afforded brassenin B (8). Corresponding 2-isomers, 21 and 23, were obtained by an analogous sequence, starting from indole-2-carboxylic acid. During the preparation of isooxobrassinin (21), which appeared to be unstable in the basic reaction medium, also an imidazo[3,4-a]indole derivative 22 has been isolated as an unexpected side product. Related oxobrassinin analogs and their 2-isomers were prepared by treatment of indol-3- and indol-2-ylcarbonyl isothiocyanate with methanol and amines. In the case of isothiocyanate 13, besides the expected products of nucleophilic addition to NCS group (monothiocarbamate 25a and thiourea derivatives 25b-25g), also the substitution products were obtained. Their formation could be explained by partial decomposition of the starting isothiocyanate to an unstable ketene, which reacts with methanol and amines to afford the corresponding methyl carboxylate 26a and carboxamides 26b-26g. Antifungal activity of the prepared compounds has been examined, using the fungus Bipolaris leersiae. All of the compounds exhibited lower activity than phytoalexin brassinin.

Keywords: Indoles; Phytoalexins; Brassinin; Methoxybrassenin B; Isothiocyanates.