Stereoselective oxidative C3-N bond dehydrogenation and aromatization of 1-carboxyl substituted tetrahydroisoquinolines employing pipecolate oxidaseOA
The dehydrogenation of C-N bond in 1,2,3,4-tetrahydroisoquinolines(THIQs),especially 1-substituted THIQs,is a type of fascinating transformation owing to its utility in synthetic organic chemistry.Yet,the existing reports are limitedly known as C1-N semi-dehydrogenation and dehydroaromatization.Herein,we describe a biocatalytic strategy for stereoselective oxidative C3-N dehydrogenation and aromatization of 1-substituted THIQs.This redox biotransformation enables the efficient kinetic resolution of a range of racemic 1-carboxyl substituted THIQs by employing a putative pipecolate oxidase from Schizosaccharomyces octosporus yFS286(SoPIPOX),providing straightforward access to aromatized isoquinolines and unreacted(R)-enantiomers with excellent enantioselectivity and regioselectivity under mild conditions.Mechanistic studies reveal that the SoPIPOX-mediated successive dehydrogenation process proceeds via the initial unusual C3-N dehydrogenation followed by spontaneous further dehydrogenative aromatization of the resultant imine intermediate.This work lays the foundation for repurposing pipecolate oxidase for the synthesis of versatile N-heterocycles analogues.
Shuyun Ju;Xiaoshu Zhou;Huanhuan Jin;Yang Yang;Lirong Yang;Jianping Wu
College of Chemical and Biological Engineering,Zhejiang University,Hangzhou,310058 Zhejiang,ChinaTransfar Chemicals Group Co.,Ltd.,Hangzhou 311215,Zhejiang,ChinaCollege of Chemical and Biological Engineering,Zhejiang University,Hangzhou,310058 Zhejiang,China ZJU-Hangzhou Global Scientific and Technological Innovation Center,Hangzhou 311200,ChinaDepartment of Chemistry and Biochemistry,University of California Santa Barbara,Santa Barbara CA 93106,USACollege of Chemical and Biological Engineering,Zhejiang University,Hangzhou,310058 Zhejiang,China ZJU-Hangzhou Global Scientific and Technological Innovation Center,Hangzhou 311200,ChinaCollege of Chemical and Biological Engineering,Zhejiang University,Hangzhou,310058 Zhejiang,China ZJU-Hangzhou Global Scientific and Technological Innovation Center,Hangzhou 311200,China
化学化工
Chiral tetrahydroisoquinolinesOxidative dehydrogenationAromatizationAsymmetric catalysisKinetic resolution
《Green Synthesis and Catalysis》 2026 (2)
P.182-187,6
supported by the National Key R&D Program of China(No.2019YFA0905000)the Postdoctoral Program of Zhejiang Province(No.ZJ2021031).
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