Synthesis of Enantiomerically Enriched 1,2,3- Triazole-derivatized Homoalanines

Abstract

In recent decades, the synthesis of amino acid – triazole conjugates has become an emerging area. L- and Dazidohomoalanine derivatives readily undergo copper(I)- catalyzed azide-alkyne dipolar cycloaddition reaction. The expected 4-substituted-1H-1,2,3-triazol-1-yl-homoalanines are obtained in the reactions of either N- and O-protected or protecting-group-free azidohomoalanines with various alkynes. 1,2,3-Triazole conjugate formation tolerates various functional groups. The synthetic approach that uses N- and O-protected starting materials relays on the standard chromatographic purification of intermediates that are further deprotected by hydrogenolysis. In this way, the purification of final products is not required. The synthetic approach that uses protecting-groupfree azidohomoalanine is faster from a synthetic point of view as it includes only one step. However, the purification of protectinggroup- free amino acid derivatives is laborious. Additionally, we have shown that the chiral stationary phase CROWNPAK® CR(+), which is based on chiral crown ether as a selector, is applicable for direct chromatographic determination of enantiomeric ratio of the title products.