earticle

영어

L-6-Hydroxynorleucine is a chiral intermediate useful for the synthesis of a asopeptidase inhibitor in clinical trials and for the synthesis of C-7 substituted azepinones as potential intermediates for other antihypertensive metalloprotease inhibitors. It has also been used for the synthesis of siderophores, indospicine, and peptide hormone analogues. Previous synthetically useful methods for obtaining this intermediate have involved synthesis of the racemic compound followed by enzymatic resolution. D-Amino acid oxidase has been used to convert the Damino
acid to the ketoacid leaving the L-enantiomer. In a second approach, racemic N-acetylhydroxynorleucine has been treated with L-amino acid acylase to give the L-enantiomer. Transaminases have good characteristics required for industrial biocatalysts such as broad
substrate specificity, high enantioselectivity, high turnover number, and no requirement for external cofactor regeneration. In the present study, branched chain aminotransfese from E. coli has been successfully used to synthesize enantiopure L-6-Hydroxynorleucine from corresponding keto acid in quantitative yields and high enantiomeric purity (e.e. > 99 %).