生物に倣うインドール酸化反応を用いた生物活性アルカロイドの全合成

DOI Web Site Web Site PubMed 参考文献42件
  • 石川 勇人
    熊本大学大学院自然科学研究科理学専攻化学講座

書誌事項

タイトル別名
  • Total Synthesis of Biologically Active Alkaloids Using Bio-inspired Indole Oxidation
  • Symposium Review 生物に倣うインドール酸化反応を用いた生物活性アルカロイドの全合成
  • Symposium Review セイブツ ニ ナラウ インドール サンカ ハンノウ オ モチイタ セイブツ カッセイ アルカロイド ノ ゼン ゴウセイ

この論文をさがす

抄録

  Many tryptophan-based dimeric diketopiperazine (DKP) alkaloids including WIN 64821 and ditryptophenaline, which exhibit fascinating biological activities, have been isolated from fungi. These alkaloids possess a unique architecture; therefore several total syntheses of these compounds have been accomplished via bio-inspired reactions. Despite these elegant strategies, we were convinced that a more direct bio-inspired solution for the preparation of tryptophan-based DKP alkaloids was possible because in a true biosynthesis, direct dimerization of tryptophan occurs in aqueous media without incorporation of a protecting group on the substrates. Thus we developed direct bio-inspired dimerization reactions in aqueous, acidic media, along with a novel biomimetic pathway, to provide C2-symmetric and non-symmetric dimeric compounds from commercially available amine-free tryptophan derivatives using Mn(OAc)3, VOF3, and V2O5 as one-electron oxidants. In addition, concise two-pot or three-step syntheses of the naturally occurring dimeric DKP alkaloids (+)-WIN 64821, (−)-ditryptophenaline, and (+)-naseseazine B were accomplished with total yields of 20%, 13%, and 20%, respectively. The present synthesis has several noteworthy features: 1) the tryptophan-based C2-symmetric and non-symmetric dimeric key intermediates can be prepared on a multigram scale in one step; 2) the developed oxidation reaction was carried out in aqueous, acidic solution without deactivation of the metal oxidants; 3) protection of the primary amine can be avoided by salt formation in aqueous acid; 4) for the total two-pot operation, the reaction media are environmentally friendly water and ethanol; 5) satisfactory total yields are obtained compared with previously reported syntheses.<br>

収録刊行物

  • 薬学雑誌

    薬学雑誌 135 (3), 383-390, 2015-03-01

    公益社団法人 日本薬学会

参考文献 (42)*注記

もっと見る

関連プロジェクト

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ