38 ヘパラナーゼ阻害活性天然物トラキスプ酸の全合成(口頭発表の部)

• 平井 加奈子

  長崎大薬

• 大井 秀訓

  長崎大薬

• 江角 朋之

  長崎大薬

• 岩渕 好治

  長崎大薬

• 畑山 範

  長崎大薬

書誌事項

タイトル別名

• 38 Total Synthesis of Trachyspic Acid, a Tumor Cell Heparanase Inhibitor

抄録

Trachyspic acid was isolated from the culture broth of Talaromyces trachyspermus SANK 12191 after screening for low molecular weight substances that exhibit heparanase inhibitory activity. This new metabolite possesses a unique spiroketal structure consisting of the 2-nonyl-3-furanone and the tetrahydrofuran having citric acid unit. However, even the relative configuration of this compound has not been determined yet. We describe the first synthesis of (±-trachyspic acid, thereby establishing its relative configuration to be 3R^*4S^*6S^*. Aldol reaction of tert-butyl 4-(p-methoxybenzyl)oxy-2-oxo-butyrate (9) and tert-butyl 4-pentenoate (10) gave (3R^*,4S^*)-11a and (3R^*,4S^*)-11b in a ratio of 3: 2. Upon silylation and oxidative cleavage of the olefinic double bond, 11a and 11b were converted to key aldehydes 12a and 12b, respectively. The crucial Ni(II)/Cr(II)-mediated reaction of 12a with triflate 16, prepared from 3-(1,3-dioxolan-2-yl)dodecan-2-one (15), turned out to occur successfully to produce adduct 17a in 84% yield. Similarly, Ni(II)/Cr(II)-mediated reaction of 12b with 16 afforded 17b in 59% yield. Upon Dess-Martin oxidation, desilylation, and HClO_4-treatment, 17a and 17b gave the corresponding spiroketal 19a and 19b in very good yields. After acetylation of 19a and 19b, the corresponding acetates were each converted to ketone 22a and 22b by a three-step sequence involving removal of the p-methoxybenzyl protecting group, oxidation of the primary alcohol, and ozonolysis of the exomethylene group. Finally, exposure of 22a and 22b to TFA furnished the corresponding tricarboxylic acid 23a and 23b, respectively. At this stage, we found that 23b was identical with trachyspic acid by ^1H NMR comparison. The trimethyl ester of 23b also exhibited spectral properties in accord with those reported for the trimethyl ester of natural trachyspic acid.

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 43 (0), 223-228, 2001

  天然有機化合物討論会実行委員会

詳細情報

• CRID: 1390282681056067968
• NII論文ID: 110006682083
• DOI: 10.24496/tennenyuki.43.0_223
• 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