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.

近年来，C_2对称手性化合物被认为是手性助剂和手性结构单元。因此，相当大的努力已经指向合成它们。已知非手性对称和双官能化底物的双重不对称反应提供了C_2对称的手性化合物，并伴有对映体增强。通过1，6-庚二烯的双不对称烯丙基硼化反应，再经氨环化和氨基甲酸酯化反应，合成了一种新型的C_2对称的2，6-二烯丙基哌啶手性结构单元。它的合成效用已经在哌啶相关生物碱的便利合成中得到证实，例如2，6-反式-二烷基哌啶，例如松树和云杉物种的成分（-）-表-二氢pinidine，和火蚁毒液的成分（2 R，6 R）-反式-solenopsin A，瓢虫防御生物碱precoccinelline，和（-）porantheridine，伞房孔菊的新三环生物碱，基于独特的去对称化，使用碘代氨基甲酸酯化作为关键步骤，沿着保护一个烯丙基。目前正在研究将这一方法进一步应用于其他生物碱，如（-）-来瑟兰定。

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 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)

高畠H.；

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。