含双环[2.2.2]辛烷和双环[2.2.1]庚烷的γ-氨基丁酸(GABA)衍生物的高效、简明合成方法

IF 1.8 3区 化学 Q3 CHEMISTRY, ORGANIC
Wen Luo , Xinqiang Cheng , Xinyuan Zhu , Yong Li , Yongjia Liu , Wenqian Huang , Yan Li , Guilong Zhao
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引用次数: 0

摘要

建立了一种高效、简洁的五步法合成含有双环[2.2.2]辛烷和双环[2.2.1]庚烷的γ-氨基丁酸(GABA)衍生物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

An efficient, concise synthetic approach to γ-aminobutyric acid (GABA) derivatives bearing bicyclo[2.2.2]octane and bicyclo[2.2.1]heptane rings

An efficient, concise synthetic approach to γ-aminobutyric acid (GABA) derivatives bearing bicyclo[2.2.2]octane and bicyclo[2.2.1]heptane rings

An efficient, concise 5-step synthetic approach to γ-aminobutyric acid (GABA) derivatives bearing bridged bicyclo[2.2.2]octane and bicyclo[2.2.1]heptane rings was developed, which consists of Diels-Alder cycloaddition to construct the bridged bicyclic rings with a nitrile functionality, hydrogenation, LDA-mediated SN2 alkylation to introduce acetate moiety at the α-position of nitrile, reduction of the nitrile functionality to amino group followed by intramolecular formation of lactam and finally acidic hydrolysis of lactam to give the desired GABA derivatives (1 and 19 as HBr salts). The reaction conditions of Diels-Alder cycloaddition and LDA-mediated SN2 alkylation were intensively optimized to improve the yields. The stereochemistry of the SN2 reaction involved in the bicyclo[2.2.1]heptane ring system was unambiguously elucidated by single-crystal X-ray diffraction. This synthetic approach possesses advantages of less reaction steps, high overall yields and avoidance of toxic reagents, and may find wide applications in the synthesis of other GABA derivatives with similar bicyclic or polycyclic rings.

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来源期刊
Synthetic Communications
Synthetic Communications 化学-有机化学
CiteScore
4.40
自引率
4.80%
发文量
156
审稿时长
4.3 months
期刊介绍: Synthetic Communications presents communications describing new methods, reagents, and other synthetic work pertaining to organic chemistry with sufficient experimental detail to permit reported reactions to be repeated by a chemist reasonably skilled in the art. In addition, the Journal features short, focused review articles discussing topics within its remit of synthetic organic chemistry.
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