Conformational study and enantioselective, regiospecific syntheses of novel aminoxy trans-proline analogues derived from an acylnitroso Diels-Alder cycloaddition

The cis/trans isomerization of the proline amide bond has many implications in biological processes. The conformations of representative acylnitroso-d erived proline analogues derived from cyclopentadiene were shown to exist e xclusively as the E or trans conformation in CD2Cl2. The energetically favo red conformations were determined using COSMO self-consistent reaction fiel d calculations at the B3LYP/6-31G* level of theory in addition to low tempe rature H-1 NMR studies. The syntheses of the acylnitroso-derived peptides u tilized two methods to selectively functionalize either of two chemically s imilar esters in the acylnitroso-derived amino acids. A novel transpeptidat ion of the amino acid that controlled the absolute stereochemistry in the a cylnitroso Diels-Alder cycloaddition took advantage of an activated aminoxy amide linkage to control regiochemistry. Alternatively, an enantioselectiv e and regiospecific enzymatic resolution of a racemic dimethyl ester provid ed a novel aminoxy acid.