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Updated: Nov 25, 2025

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
Published on: August 22, 2018
A Reliable Enantioselective Route to Mono-Protected N1-Cbz Piperazic Acid Building Block
Evanthia Papadaki1, Dimitris Georgiadis1, Michail Tsakos1
1Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, 15771 Athens, Greece.
Abstract:
The chiral N1-Cbz, N2-H derivative of the piperazic acid monomer is a valuable building block in the total synthesis of natural products, comprising this nonproteinogenic amino acid. In that context, we wish to report an improved synthetic protocol for the synthesis of both (3R)- and (3S)-piperazic acids bearing the carboxybenzyl protecting group (Cbz) selectively at the N1 position. Our method builds on previously reported protocols, circumventing their potential shortcomings, and optimizing the ultimate selective deprotection at the N2 position, thus, offering an efficient and reproducible pathway to suitably modified piperazates in high optical purity.
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