Expedient Solution-Phase Synthesis and NMR Studies of Arylopeptoids

The development of a highly convenient and efficient protocol for iterative solution-phase synthesis of shorter oligomers of para-and meta-arylopeptoids is described. Peptide coupling methods for accessing longer oligomers were studied: use of the new coupling reagent COMU was found to be the most efficient for creation of the tertiary benzamide bonds. The cis/trans isomerism of arylopeptoid backbones was studied by NMR and was found to be highly dependent on the nature of the side chains. Increasing bulkiness of the side chains favored the cis amide bond conformation; arylopeptoids possessing tert-butyl side chains contained exclusively cis amide bonds.