Current Topics in Medicinal Chemistry

Allen B. Reitz
Fox Chase Chemical Diversity Center, Inc.
Doylestown, PA
USA

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

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

Affiliation: Departamento de Quimica, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional, Apartado Postal 14-740, 07000 Mexico D. F., Mexico.

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

Graphical Abstract:


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.

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Article Details

VOLUME: 14
ISSUE: 10
Page: [1257 - 1270]
Pages: 14
DOI: 10.2174/1568026614666140423110420