Development of New Reactivities of Indole Nucleus and its Application to Syntheses of Natural Products

吲哚核新反应活性的开发及其在天然产物合成中的应用

• 批准号: 12672069
• 负责人: MURAKAMI Yasuoki
• 金额: $ 2.05万
• 依托单位: Toho University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672069/
• 关键词: canthine-6-one; indole; lysergic acid; Reissert indole synthesis; benztryptophan; acylindole; alkylindole; Heck reaction; ベンズインドール; 閉環反応; β-カルボリン; リゼルギン酸; キノロン; バッカクアルカロイド; DMAT; ene-diamine; N-acylation; スルホンアミド

We obtained the following result by studying the titled project.1) We found that quinolone was unexpectedly obtained rather the expected 7-substituted indole in the reduction of 1, 2, 3-trisubstituted nitropyruvate in Reissert indole synthesis2) A variety of approach have been done for the synthesis of lysergic acid. Effort was mainlly focused on the construction of C-ring having nitrogen-containing substituent and simultaneous construction of C and D rings. However synthesis of lysergic acid was not acieved yet. The first synthesis of optically active DMAT, an intermediate of ergot alkaloid was successful3) In relation with the synthesis of lysergic acid, syntheses of new acylating reagents having o-substituted diacylaniline structure and of new ligands for metal-catalysts having asymmetric C-N axis were successful4) We examined to develop new type of reaction in ethyl indole-2-carboylates and to apply them for synthesis of useful substance; I.e., a) convenient synthesis of canthine-6-one using efficient aldol condensation of 1-formyl-β-carboline with ethyl acetate, b) removal of 3-acyl group in indole-2- carboxylates under acidic condition where 3- acylindole has C4- substituent, c) new convenient method to convert 3-acyl group in indoles to 3-alkyl group by catalytic reduction under acidic condition5) We found that existence of 1 and 4-methyl group in N-alkylterahydrocrabazole affects the products distribution in Vilsmeier-Haak reaction. We found new knoledge that in 4, 4-dimethyl compound the products formed due to cleavage of 4-4a bond was formed6) The short and convenient synthesis of benz[g]tryptophan was developed by the reaction of benz[g]indole with serine

通过对课题的研究，我们得到了以下结果：1）在Reissert吲哚合成中，我们发现在还原1，2，3-三取代硝基丙酮酸的反应中，出乎意料地得到了喹诺酮，而不是预期的7-取代吲哚。主要工作集中在含氮取代基的C环的构建和C、D环的同时构建。但麦角酸的合成尚未完成。首次成功合成了麦角生物碱中间体DMAT（光学活性）; 3）在麦角酸的合成中，成功合成了具有邻取代二酰基苯胺结构的新型酰化试剂和具有不对称C-N轴的新型金属催化剂配体;即，B）在酸性条件下除去吲哚-2-羧酸酯中的3-酰基，其中3-酰基吲哚具有C4-取代基，c）酸性条件下催化还原吲哚中的3-酰基转化为3-烷基的简便新方法5）我们发现1和4-N-烷基四氢克巴唑中的甲基影响Vilsmeier-Haak反应的产物分布。发现了4，4-二甲基化合物中4-4a键断裂生成的产物是新的发现。6）通过苯并[g]吲哚与丝氨酸反应，发展了苯并[g]色氨酸的简便合成方法

项目成果

H, Hikawa: "A Short Synthesis of Optically Active dimethyl-Allyltryptophan (DMAT)"Synthesis. 214-216 (2000)

H，Hikawa：“光学活性二甲基烯丙基色氨酸（DMAT）的简短合成”合成。

Y. Yokoyama, K. Osanai, M. Mitsuhashi, K. Kondo, Y. Murakami: "An Effcent Method of Synthesizing Optically Pure N-Boc-4-bromoN-methyl-1-tosyl-D-tryptophan Methyl Easter, a Key Intermdeiate in the Synthesis of Opticallly Active Ergot Alkaloids"Heterocycles

Y. Yokoyama、K. Osanai、M. Mitsuhashi、K. Kondo、Y. Murakami：“合成光学纯 N-Boc-4-溴N-甲基-1-甲苯磺酰基-D-色氨酸甲基复活节的有效方法，关键

Y. Yokoyama, H. Hikawa, Y. Murakami: "Does Water Suppress the Racemization and Decomposition of Amino Acids?"J.Chem.Soc.Perkin Trans.1. ・12. 1431-1434 (2001)

Y. Yokoyama、H. Hikawa、Y. Murakami：“水会抑制氨基酸的外消旋化和分解吗？”J.Chem.Soc.Perkin Trans.12.1431-1434

H. Suzuki, T. Furukawa, C. Yamada, I. Shibuya, M. Kurumi, T. Yokoyama, Y. Murakami: "Synthesis of Non-peptidic Tryptamine Derivative (THS-12) Which Stimulates TPO Responsive Cell Growth (Synthetic Studies on Indoles and Related Compounds 51)"Heterocycles.

H. Suzuki、T. Furukawa、C. Yamada、I. Shibuya、M. Kurumi、T. Yokoyama、Y. Murakami：“刺激 TPO 反应性细胞生长的非肽色胺衍生物 (THS-12) 的合成（合成研究）

K.Kondo: "Chiral Axis due to an Acyclic Imide-Ar Bond : a Study of Steric Effects of Acyl Groups on Racemization"Tetrahedron. 56. 8883-8891 (2000)

K.Kondo：“无环酰亚胺-Ar 键产生的手性轴：酰基对外消旋化的空间效应的研究”四面体。