Enantiopure 1,2,3-Triazolyl-β-amino Acids via Click Cycloaddition Reaction on Racemic Alkynyl Precursors Followed by Separation of Stereoisomers

Title:Enantiopure 1,2,3-Triazolyl-β-amino Acids via Click Cycloaddition Reaction on Racemic Alkynyl Precursors Followed by Separation of Stereoisomers

Volume: 14 Issue: 10

Author(s): Margarita Escudero-Casao, Alberto Vega-Penaloza and Eusebio Juaristi

Affiliation:

Keywords: Triazol, click-reaction, β-amino acids, peptidomimetics, enantio- and diastereoseparation.

Abstract: In recent years, peptidomimetics have gained enormous importance in drug design aiming to achieve increased drug metabolic stability and higher selectivity. In the field of peptidomimetics, β-peptides incorporating β²- and β³-amino acids (the higher homologs of natural α-amino acids) provide a powerful method for the synthesis of peptidomimetics with particular secondary structures. In this regard, 1,2,3-triazole-modified peptidomimetics can act as effective peptide surrogates, and therefore have gained considerable attention. In the present report, 1,4-disubstituted 1,2,3-triazoles attached to β-amino acids were prepared selectively from the corresponding alkynyl-β²-amino acids according to Huisgen’s copper-catalyzed 1,3-dipolar cycloaddition (CuAAC), under mild conditions and with very high efficiency. Different azide derivatives, including some incorporating α-amino acids, were employed in this cycloaddition reaction. The enantiopure compounds were obtained via diastereomeric salt formation with chiral adjuvants, and subsequent separation.

Cite this article as:

Escudero-Casao Margarita, Vega-Penaloza Alberto and Juaristi Eusebio, Enantiopure 1,2,3-Triazolyl-β-amino Acids via Click Cycloaddition Reaction on Racemic Alkynyl Precursors Followed by Separation of Stereoisomers, Current Topics in Medicinal Chemistry 2014; 14 (10) . https://dx.doi.org/10.2174/1568026614666140423110420