Enantioselective Nitration of Chiral (E)-Crotylsilanes: A Concise Asymmetric Synthesis of (E)-Olefin Dipeptide Isosteres

摘要

Replacement of the amide bond linkage with an (E)-olefin is a proven useful configurationally biased structural mimic for the construction of peptide linkages in a number of different enzyme inhibitors. These analogs of biologically active peptides offer distinct advantages over the naturally occurring compounds, including lower enzymatic degradation, increased oral bioavailability, and a prolonged duration of action. The amide linkage is the primary target for enzymatic degradation; therefore, structural modifications at this site may lead to enhanced metabolic stability. In addition, interest has emerged in peptidomimetics of inverse D-peptides which are resistant to the action of cellular proteases, thereby making them attractive drug candidates. The structural similarities between the contributing resonance structures of the amide linkage and the incorporated (E)-olefin iaostere produced in this study are illustrated in eq 1.