- Synthesis of 2,6,7-Trisubstituted Prenylated indole
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Prenylated indole alkaloids bearing more than one prenyl or reverse-prenyl group show various biological activities. Among them, synthesis of trisubstituted-type prenylated indoles have not been well explored because of the difficulty in regioselective introduction of multiple prenyl and reverse-prenyl groups due to steric hindrance problems. Herein, we describe a synthesis of 2,6,7-trisubstituted prenylated indole using aza-Claisen rearrangement under mild conditions to introduce a prenyl group at C7 in the presence of the prenyl group at C6.
- Shiozawa, Motoki,Iida, Keisuke,Odagi, Minami,Yamanaka, Masahiro,Nagasawa, Kazuo
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- Isolation, structural elucidation and biosynthesis of 3-hydroxy-6- dimethylallylindolin-2-one, a novel prenylated indole derivative from Actinoplanes missouriensis
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Many prenylated indole derivatives are widely distributed in nature. Recently, two Streptomyces prenyltransferases, IptA and its homolog SCO7467, were identified in the biosynthetic pathways for 6-dimethylallylindole (DMAI)-3-carbaldehyde and 5-DMAI-3-acetonitrile, respectively. Here, we isolated a novel prenylated indole derivative, 3-hydroxy-6-dimethylallylindolin (DMAIN)-2-one, based on systematic purification of metabolites from a rare actinomycete, Actinoplanes missouriensis NBRC 102363. The structure of 3-hydroxy-6-DMAIN-2-one was determined by HR-MS and NMR analyses. We found that A. missouriensis produced not only 3-hydroxy-6-DMAIN-2-one but also 6-dimethylallyltryptophan (DMAT) and 6-DMAI when grown in PYM (peptone-yeast extract-MgSO 4) medium. We searched the complete genome of A. missouriensis for biosynthesis genes of these compounds and found a gene cluster composed of an iptA homolog (AMIS-22580, named iptA -Am) and a putative tryptophanase gene (AMIS-22590, named tnaA -Am). We constructed a tnaA -Am -deleted (ΔtnaA -Am) strain and found that it produced 6-DMAT but did not produce 6-DMAI or 3-hydroxy-6-DMAIN-2-one. Exogenous addition of 6-DMAI to mutant ΔtnaA -Am resulted in the production of 3-hydroxy-6-DMAIN-2-one. Furthermore, in vitro enzyme assays using recombinant proteins produced by Escherichia coli demonstrated that 6-DMAI was synthesized from tryptophan and dimethylallyl pyrophosphate in the presence of both IptA -Am and TnaA -Am, and that IptA -Am preferred tryptophan to indole as the substrate. From these results, we concluded that the iptA -Am -tnaA -Am gene cluster is responsible for the biosynthesis of 3-hydroxy-6-DMAIN-2-one. Presumably, tryptophan is converted into 6-DMAT by IptA -Am and 6-DMAT is then converted into 6-DMAI by TnaA -Am. 6-DMAI appears to be converted into 3-hydroxy-6-DMAIN-2-one by the function of some unknown oxidases in A. missouriensis.
- Satou, Ryutaro,Izumikawa, Miho,Katsuyama, Yohei,Matsui, Misato,Takagi, Motoki,Shin-Ya, Kazuo,Ohnishi, Yasuo
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