43 発癌プロモーター・インドラクタム誘導体の微生物転換を利用した合成と構造活性相関(口頭発表の部)

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Teleocidins are potent tumor promoters produced by actinomycetes. (-)-Indolactam-Val (ILV), which has the fundamental structure of teleocidins and is the minimum unit for tumor-promoting activity, is useful as a lead compound for structure-activity studies and receptor analysis. Hitherto, total syntheses of ILV and its analogues have been intensively investigated. However, more convenient syntheses are desirable from the view point of synthesizing various indolactam congeners for structure-activity studies. We have demonstrated that ILV was biosynthesized from L-Trp, L-Val and L-Met via N-Me-L-Val-L-Trp-ol using Streptoverticillium blastmyceticum NA34-17. Since N-Me-L-Val-L-Trp-ol can be chemically synthesized without difficulty, utilization of the microbial cyclization enzyme would be a convenient synthetic method of various indolactam analogues for structure-activity studies. We have metabolized twelve synthetic seco-compounds and obtained ten ILV congeners with L-Ala, Abu, γ,δ-Δ-Nva, Nva, Nle, tert-Leu, Leu, Ile, allo-Ile, Phg, instead of L-Val in ILV. These indolactam congeners were examined for two biological tests related to tumor promotion. They were binding ability to the 12-O-tetradecanoylphorbol-13-acetate receptor and stimulation of radioactive inorganic phosphate incorporation into phospholipids of HeLa cells. The results indicated that both the hydrophobicity and the bulkiness of the substituents at position 12 increased these activities, demonstrating the recent hypothesis that the isopropyl group at position 12 of ILV is involved in the hydrophobic interaction on the receptor site.
天然有機化合物討論会の論文
1991-09-07

43 発癌プロモーター・インドラクタム誘導体の微生物転換を利用した合成と構造活性相関(口頭発表の部)

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