Synthesis 2023; 55(13): 2005-2010
DOI: 10.1055/a-2039-6180
paper

Enantioselective Synthesis of (R)-Tiagabine via Asymmetric Hydrogen Atom Transfer Protocol

Longfei Li
,
Wanjiao Chen
,
Zhongyun Xu
,
Jie Jiang
,
Yong-Qiang Zhang
We thank the National Natural Science Foundation of China (NSFC, No. 21901143), the Taishan Scholar Program of Shandong Province (No. tsqn201909006), the Young Scholars Program of Shandong University (11190089964157) and the Natural Science Foundation of Shandong Province (ZR2021QB118).


Abstract

An enantioselective synthesis of tiagabine has been achieved utilizing an asymmetric hydrogen atom transfer protocol to construct its essential chiral tertiary carbon center. A cyclization reaction via double N-substitution is tactically orchestrated as the other key step to install the crucial alkaloid ring. Compared with the previous synthetic strategy, which used commercially available nicotinate as the starting material to ensure a short synthetic route, this strategy uses a readily modifiable and accessible alkyl-substituted acrylate as the starting material and thus provides a scenario for the facile synthesis of analogues and derivatives of tiagabine for further biological research.

Supporting Information



Publication History

Received: 23 October 2022

Accepted after revision: 21 February 2023

Accepted Manuscript online:
21 February 2023

Article published online:
20 March 2023

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