Self-Assembly of Noncyclic Bis-d- and l-tripeptides into Higher Order Tubular Constructs: Design, Synthesis, and X-ray Crystal Superstructure

Trans (1R,2R)-diaminocyclohexane was used as a semirigid vicinal diamine to anchor two N-protected
tripeptides consisting of l-d-l amino acids as carboxy terminal amides. The bis-tripeptide consisting of
l-Ser (OBn)-d-Ser (OBn)-l-Ser (O-p-bromobenzyl) Boc afforded X-ray quality crystals containing benzene
and chloroform solvent molecules. Analysis of the solid-state structure revealed a highly H-bonded helical
open-ended tubular superstructure. The tripeptide strands intertwine like a pair of self-embracing arms,
held together by a γ-turn and a 14-membered antiparallel H-bonded macroring spanning the first and
third amino acid residues within each strand. Whereas the tripeptide from the R,R anchor gave beautiful
crystals from benzene and chloroform, the analogous construct from the S,S-anchored diamine gave a
gel. Related bis-tripeptides with different amino acids showed extensive intramolecular H-bonding based
on NMR titration and dilution experiments.