Solution- and solid-phase synthesis of triazole oligomers that display protein-like functionality

(Chemical Equation Presented) We recently developed a new class of oligomers that contain α-amino acid residues linked by 1,2,3-triazole groups [Angelo, N. G.; Arora, P. S. J. Am. Chem. Soc. 2005, 127, 17134-17135]. Synthesis of these oligomers involves an iterative sequence consisting of diazotransfer and Huisgen 1,3-dipolar cycloaddition steps. In this contribution, we describe an efficient one-pot, two-step sequence for the preparation of triazoles from the corresponding amino acid-derived amines and alkynes in solution. The one-pot sequence affords the desired products in significantly higher yields than our original method. We also outline a highly effective protocol for the synthesis of these triazole-based biomimetic oligomers on the solid phase. We find that amino acid derivatives and iterative formation of triazole rings require nontraditional reaction conditions for high yields.