Synthesis of Enantiomerically Pure 6-Substituted-Piperazine-2-Acetic Acid Esters as Intermediates for Library Production

The Journal of Organic Chemistry
Srinivas ChamakuriDamian W Young

Abstract

The piperazine heterocycle is broadly exploited in FDA-approved drugs and biologically active compounds, but its chemical diversity is usually limited to ring nitrogen substitutions, leaving the four carbon atoms underutilized. Using an efficient four-step synthesis, chiral amino acids were transformed into 6-substituted piperazine-2-acetic acid esters as diastereomeric mixtures whose cis and trans products could be chromatographically separated. From six amino acids (both antipodes), a complete matrix of 24 monoprotected chiral 2,6-disubstituted piperazines was obtained, each as a single absolute stereoisomer in multigram quantities. These diverse and versatile piperazines can be functionalized on either nitrogen atom, allowing them to be used as scaffolds for parallel library synthesis or intermediates for the production of novel piperazine compounds.

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Citations

Apr 25, 2019·Organic & Biomolecular Chemistry·Paige Dickson, Thomas Kodadek
Oct 30, 2020·Organic & Biomolecular Chemistry·Srinivas ChamakuriDamian W Young
Sep 6, 2018·The Journal of Organic Chemistry·Shiva Krishna Reddy GuduruDamian W Young

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