Synthesis of C_2- symmetric α, α'-disubstituted azacycloalkanes as chiral building blocks and their application

C_2-对称α,α-二取代氮杂环烷烃手性结构单元的合成及其应用

• 批准号: 12672050
• 负责人: TAKAHATA Hiroki
• 金额: $ 1.98万
• 依托单位: Tohoku Pharmaceutical University (2001-2002)Toyama Medical and Pharmaceutical University (2000)
• 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-12672050/
• 关键词: double asymmetric allylboration; C_2 symmetrically chiral building block; alkaloid; asymmetric synthesis; substituted piperidine; 置換ピロリジン; 二重不斉アリルホウ素化; ピペリジン; ピロリジン; C_2対称; キラル素子; インドリチジン

Recently, C_2 symmetric chiral compounds have been recognized as chiral auxiliary and chiral building block. Therefore, considerable effort has been directed toward synthesizing them. It is known double asymmetric reaction of achiral symmetric and bifunctionalized substrate provided C_2 symmetric chiral compounds accompanied with enantiomeric enhancements. We explored a novel C_2 symmetric 2, 6-diallylpiperidine as a chiral building block via the double asymmetric allylboration of 1, 6-heptadiene followed by aminocyclization and carbamation. Its synthetic utility has been demonstrated in the expedient synthesis of piperidine-related alkaloids such as of 2, 6-trans-dialkylpiperidines such as (-)-epi-dihydropinidine, a constituent of pine and spruce species, and (2R, 6R)-trans-solenopsin A, a constituent of fire-ant venom, precoccinelline, a ladybug defense alkaloid, and (-) porantheridine, a novel tricyclic alkaloid of Poranthera corymbosa, based on distinctive desymmetrization using iodocarbamation as a key step, along with the protection of one allyl group. Further application of this procedure to other alkaloids such as (-)-lythrandine is currently under investigation.

最近，C_2对称手性化合物已被认为是手性辅助和手性构件。因此，人们付出了相当大的努力来合成它们。已知非手性对称和双官能化底物的双重不对称反应提供伴随对映体增强的C_2对称手性化合物。我们通过 1, 6-庚二烯的双不对称烯丙基硼化，然后进行氨环化和氨基甲酸酯化，探索了一种新型 C_2 对称 2, 6-二烯丙基哌啶作为手性结构单元。其合成效用已在哌啶相关生物碱的便捷合成中得到证实，例如 2, 6-反式-二烷基哌啶，如 (-)-表-二氢哌啶（松树和云杉树种的成分）和 (2R, 6R)- trans-solenopsin A（火蚁毒液的成分）、precoccinelline（一种瓢虫防御生物碱）和 (-) porantheridine（一种Poranthera corymbosa 的新型三环生物碱，基于使用碘氨基甲酸酯化作为关键步骤的独特去对称作用，以及一个烯丙基的保护。目前正在研究将此过程进一步应用于其他生物碱，例如 (-)-lythrandine。

项目成果

Takahata, H, Ouchi, H, Ichinose, M, Nemoto, H.: "A novel C2-symmetric 2,6-diallypiperidine carboxylic acid methyl ester as a promising chiral building block for piperidine-related alkaloids"Organic Letters. 4・20. 3459-3462 (2002)

Takahata, H, Ouchi, H, Ichinose, M, Nemoto, H.：“一种新型 C2 对称 2,6-二烯丙基哌啶甲酸甲酯，作为哌啶相关生物碱的有前途的手性结构单元”有机快报 4·20。 .3459-3462 (2002)

Takahata, H., Ouchi, H., Ichinose, M., Nemoto, H.: "A novel C2-symmetric 2,6-diallylpiperidine carboxylic acid methyl ester as a promising chiral building block for piperidine-related alkaloids"Organic Letters. 4. 3459-3462 (2002)

Takahata, H.、Ouchi, H.、Ichinose, M.、Nemoto, H.：“一种新型 C2 对称 2,6-二烯丙基哌啶甲酸甲酯，作为哌啶相关生物碱的有前途的手性结构单元”有机快报。

Takahata, H.; Ouchi, H.; Ichinose, M.; Nemoto, H.: "A novel C_2-symmetric 2, 6-diallylpiperidine carboxylic acid methyl ester as a promising chiral building block for piperidine-related alkaloids"Organic Letters. 4(20). 3459-3462 (2002)

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