Synergy between catalysts: enzymes and bases. DKR of non-natural amino acids derivatives

Abstract

A double catalyst system (protease + base) is applied for the dynamic kinetic resolution (DKR) of amino acid thioesters in hydrolysis, transesterification or transamidation, allowing to obtain L-N-Boc-aminoacids, esters or amides in high yields and ee. This approach not only obviates the tedious recycling steps of the undesired remaining enantiomer, but, more importantly, the enantiomeric excess of the product (ee) is independent of the extent of conversion, and the process becomes more enantiospecific compared to a kinetic resolution. Substrates of different α-C acidity can be transformed by selecting the base of appropriate strength. Conditions have been found to extend the DKR of phenylglycine thioesters to the whole set of aminoacids thioesters fully representative of natural and non-natural amino acid structures.