Solid-Phase Synthesis of 1,3-Azole-Based Peptides

Significance

A highly efficient procedure to prepare oxazoles and thiazoles on solid support from readily available amino acids was developed. Thus, the Dess-Martin oxidation of resin-bound dipeptides 1a-d gave β-keto amide derivatives 2a-d. Oxazole derivatives 3a-d were obtained by dehydrative cyclization of the β-keto amides 2a-d using triphenylphosphine in the presence of iodine and diisopropylethylamine. Treatment of resin 3 with TFA gave 5-methyloxazole-based dipeptides 4a-d with good crude purity (67-78%) and in high yield (80-93%) over six steps. The β-keto amides 2a-d were also transformed into resin-bound thiazoles 5a-d using Lawesson’s reagent. The thiazole-based peptides 6a-d were readily isolated after TFA-mediated cleavage from the corresponding resin-supported thiazoles 5 in moderate yield (50-59% over six steps).