Chemical Synthesis of marine pyrrole alkaloids effective against multidrug-resistant cancers

化学合成有效对抗多重耐药癌症的海洋吡咯生物碱

• 批准号: 14580612
• 负责人: IWAO Masatomo
• 金额: $ 2.24万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14580612/
• 关键词: multidrug-resistant cancer; marine pyrrole alkaloids; lamellarin G trimethyl ether; lamellarin D; lamellarin L; lamellarin N; permethyl storniamide A; ningalin B; 多剤耐性克服作用; 海洋天然物; ピロールアルカロイド; ラメラリンD; ラメラリンL; ラメラリンN; 多剤耐性ガン; 海洋アルカロイド; 化学合成

We have developed an efficient procedure for the synthesis of 3,4-diarylpyrrole-type marine alkaloids, which exhibit cytotoxic activity against multidrug-resistant(MDR) cancer cells.Hinsberg-type condensation of N-alkyliminodiacetates with dimethyl oxalate produced N-alkyl-3,4-dihydroxypyrrole-2,5-dicarboxylates. The bistriflate derivatives of the 3,4-dihydroxypyrroles were cross-coupled with a wide range of arylboronic acids in the presence of Pd(0) catalysts to give the 3,4-diarylpyrrole-2,5-dicarboxylates in excellent yields. The stepwise introduction of different aryl groups at the 3- and 4-positions was found to be feasible. These procedures were successfully applied for the total syntheses of lamellarin G trimethyl ether, lamellarins D,L,and N. Formal syntheses of permethyl storniamide A and ningalin B were also achieved.

以N-烷基亚氨基二乙酸酯和草酸二甲酯为原料，通过Hinsberg型缩合反应合成了N-烷基-3，4-二羟基吡咯-2，5-二羧酸酯。在Pd（0）催化剂存在下，3，4-二羟基吡咯的双三氟甲磺酸酯衍生物与多种芳基硼酸发生交叉偶联反应，得到3，4-二芳基吡咯-2，5-二羧酸酯，产率高。发现在3-和4-位上逐步引入不同的芳基是可行的。这些方法已成功地应用于片螺素G三甲基醚、片螺素D、L和N的全合成。全甲基storniamide A和ningalin B的合成也实现了形式化。

项目成果

Enantioselective synthesis of planar chiral azaferrocenes via chiral ligand-mediated ring- and lateral lithiations

通过手性配体介导的环和横向锂化对映选择性合成平面手性氮杂二茂铁

• 发表时间: 2003
• 期刊: Tetrahedron Letters 44・40
• 作者: T.Fukuda;K.Imazato;M.Iwao
• 通讯作者: M.Iwao

岩尾正倫, 福田勉: "位置選択的リチオ化反応を利用したインドール誘導体の効率的官能化"有機合成化学協会誌. 60・7. 691-700 (2002)

Masato Iwao，Tsutomu Fukuda：“利用区域选择性锂化反应对吲哚衍生物进行高效官能化”，合成有机化学学会杂志 60・7（2002）。

Asymmetric synthesis of 3-substitutes 3,4-dihydroidocoumarins via stereoselective addition of laterally lithiated chiral 2-(ο-tolyl)oxazolines to aldehydes followed by diastereomer-selective lactonization

通过将侧向锂化手性 2-(ο-甲苯基)恶唑啉立体选择性加成到醛上，然后进行非对映体选择性内酯化，不对称合成 3-取代 3,4-二氢香豆素

• 发表时间: 2005
• 期刊: Tetrahedron 61・13
• 作者: Y.Kurosaki;T.Fukuda;M.Iwao
• 通讯作者: M.Iwao

Fumito Ishibashi, Shinji Tanabe, Tatsuya Oda, Masatomo Iwao: "Synthesis and Structure-Activity Relatioship Study of Lamellarin Derivatives"Journal of Natural Products. 65・4. 500-504 (2002)

Fumito Ishibashi、Shinji Tanabe、Tatsuya Oda、Masatomo Iwao：“板层素衍生物的合成和结构活性关系研究”天然产物杂志 65・4（2002）。

Asymmetric synthesis of 3-substituted 3,4-dihydroisocoumarins via stereoselective addition of laterally lithiated chiral 2-(o-tolyl)oxazolines to aldehydes followed by diastereomer-selective lactonization

• DOI: 10.1016/j.tet.2005.01.103
• 发表时间: 2005-03
• 期刊: Tetrahedron
• 影响因子: 2.1
• 作者: Yuji Kurosaki;T. Fukuda;M. Iwao