ON THE STACKING OF BETA-RINGS - THE SOLUTION SELF-ASSOCIATION BEHAVIOR OF 2 PARTIALLY N-METHYLATED CYCLO(HEXALEUCINES)

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 beta-rings in solution. In appropriate solvents, 1 and 2 formed dimers consisting of two beta-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 beta-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 beta-rings.