40 海洋動物タツナミガイから得られた新規細胞毒性物質、ドラスタチンG、H、イソドラスタチンHの構造と合成研究(口頭発表の部)

• 武藤 毅

  名大理

• 近藤 隆史

  名大理

• 柴田 拓伸

  名大理

• 曽根 大紀

  名大理

• 藤田 達也

  名大理

• 桐生 稔

  名大理

• 木越 英夫

  名大理

• 小鹿 一

  名大理

• 山田 靜之

  名大理

書誌事項

タイトル別名

• 40 Structures and Synthetic Study of Dolastatins G and H and Isodolastatin H, Cytotoxic Compounds Isolated from the Sea Hare Dolabella auricularia.

抄録

Constituents of the Japanese sea hare Dolabella auricularia collected in Mie Prefecture, Japan were examined by using bioassay, and new cytotoxic depsipeptides, dolastatins G (1) and H (14) and isodolastatin H (15) were isolated. Dolastatin G (1) showed cytotoxicity against HeLa-S_3 cells with an IC_<50> of 1.0μg/mL. On the basis of 2D NMR technique, dolastatin G (1) has proved to be a 35-membered cyclic depsipeptide which consists of a hexapeptide and two new hydroxy acids. The absolute stereochemistry of the hexapeptide moiety was determined by the chiral HPLC analysis of amino acids obtained by acidic hydrolysis of dolastatin G (1). The absolute stereochemistry of two hydroxy acid parts was determined by the enantioselective synthesis of two corresponding fragments obtained by degradation of dolastatin G (1). For the purpose of confirming the stereostructure of dolastatin G (1), synthetic studies on dolastatin G (1) have been carried out. Three subunits, 7, 10, and 11, were synthesized, coupling of which gave seco acid 13. The synthesis of dolastatin G (1) from seco acid 13 is in progress. A 1:1 mixture of dolastatin H (14) and isodolastatin H (15) showed potent cytotoxicity against HeLa-S_3 cells with an IC_<50> of 0.00381μg/mL. On the basis of spectroscopic data, dolastatin H (14) has proved to be a linear tetrapeptide which contains two unusual amino acids and is esterified at the C-terminus by the primary hydroxyl group of 3-phenyl-1,2-propanediol. Isodolastatin H (15) is the structural isomer of dolasatin H (15), in which the tetrapeptide is esterified at the C-terminus by the secondary hydroxyl group of 3-phenyl-1,2-propanediol. The absolute stereochemistry of dolastatin H (14) and isodolastatin H (15) was unambiguously determined by the enantioselective total synthesis.

収録刊行物

• 天然有機化合物討論会講演要旨集

  天然有機化合物討論会講演要旨集 37 (0), 230-235, 1995

  天然有機化合物討論会実行委員会

詳細情報

• CRID: 1390282681054744576
• NII論文ID: 110006679415
• DOI: 10.24496/tennenyuki.37.0_230
• ISSN: 24331856
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可