On the Stacking of β ‐Rings: The solution self‐association behavior of two partially <i>N</i>‐methylated cyclo(hexaleucines)

Abstract

Abstract Cyclo(‐ D ‐Leu‐ L ‐MeLeu‐ D ‐Leu‐ L ‐MeLeu‐ D ‐Leu‐ L ‐MeLeu‐) ( 1 ) and cyclo(‐ L ‐Leu‐ D ‐Leu‐ L ‐MeLeu‐ D ‐Leu‐ L ‐Leu‐ D ‐Leu‐) ( 2 ) were synthesized and used for a study of the interaction of β ‐rings in solution. In appropriate solvents, 1 and 2 formed dimers consisting of two β ‐rings connected through six interannular H‐bonds and having the N ‐Me group(s) on the solvent‐exposed face. The study also afforded indications that 2 formed different dimers of this kind, differing in the relative orientation of the two β ‐rings. These experimental observations provide strong support to the idea that unsubstituted D , L ‐alternating cyclooligopeptides, such as cyclo(hexaleucine), can self‐assemble and give rise to long tubular stacks of β ‐rings.