A versatile route towards 6-arylpipecolic acids

Pipecolic acid is known as a non-proteinogenic amino acid with a secondary amine. It contains a six-membered ring and is, like its five-membered correlate, known for its secondary structure inducing properties, which are particularly useful in the design of peptide conformations. We present a new an...

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Bibliographic Details
Main Authors: Erich Gebel, Cornelia Göcke, Carolin Gruner, Norbert Sewald
Format: Article
Language:English
Published: Beilstein-Institut 2025-06-01
Series:Beilstein Journal of Organic Chemistry
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Online Access:https://doi.org/10.3762/bjoc.21.88
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Summary:Pipecolic acid is known as a non-proteinogenic amino acid with a secondary amine. It contains a six-membered ring and is, like its five-membered correlate, known for its secondary structure inducing properties, which are particularly useful in the design of peptide conformations. We present a new and improved way to generate enantiomerically pure pipecolic acid derivatives with aryl modifications in C6 position by utilising the chiral pool of a non-proteinogenic amino acid in combination with transition metal-catalysed cross-coupling reactions. Moreover, we present an in-depth NMR analysis of the key intermediate steps, which illustrates the conformational constraints in accordance with coupling constants and resulting dihedral angles.
ISSN:1860-5397