Synthetic Approaches to Bis-Peptides Attached on Polynorbornane Molecular Scaffolds with Well-Defined Relative Positions and Distances

This paper describes novel synthetic approaches to polynorbornane molecular scaffolds substituted with peptides at various, well-defined positions. A library of norbornene building blocks with attached peptides was prepared. Alkene cyclobutane epoxide (ACE) coupling method was used as a key step reaction for connecting of two norbornene building blocks into bis-peptide scaffolds. Photodimerization of cyclobutene diesters offers alternative route to polynorbornane bis-peptides. Pyrrolo-peptides were used for preparation of peptide substituted 7-aza norbornenes. Unsymmetrical bis-peptide scaffolds were prepared by ACE coupling of peptide-norbornane epoxide with another norbornene-peptide block. Chemical elaboration of bridgehead dimethyl esters of ACE products or epoxide ACE reagents was also used for peptide attachment.