Synthesis and Evaluation of Novel Activated Mixed Carbonate Reagents for the Introduction of the 2-(Trimethylsilyl)ethoxycarbonyl(Teoc)-Protecting Group

The synthesis of 1-[2-(trimethylsilyl)ethoxycarbonyloxy]benzotriazole (Teoc-OBt) and 1-[2-(trimethylsilyl)ethoxycarbonyloxy]pyrrolidin-2,5-dione (Teoc-OSu) in high yields is reported. Both compounds are crystalline compounds that react with amino acids under Schotten-Baumann conditions to produce Teoc-amino acids in high yields. The synthesis of nine new Teoc-amino acid derivatives is reported. Analysis of the products obtained during the synthesis of Teoc-Phe before and after crystallization as the cyclohexylamine salt revealed that ~ 5% of the corresponding dipeptide, Teoc-Phe-Phe-OH was produced when Teoc-OBt was used as the acylating reagent. In contrast, no dipeptide was detected when Teoc-OSu was utilized as the acylating reagent for the synthesis of the Teoc-amino acid derivatives studied. The use of Teoc-OSu should facilitate the use of the Teoc-group in peptide synthesis.