SYNTHESIS OF PEPTIDES AND PSEUDOPEPTIDES INCORPORATING AN ENDO-(2S,3R)-NORBORN-5-ENE RESIDUE AS A TURN INDUCER

The desymmetrization of endo-norborn-5-ene-2,3-dicarboxylic anhydride (5) by proline derivatives is used to prepare peptides and pseudopepti des incorporating an endo-(2S,3R)-2-amino-3-carboxynorborn-5-ene (1) r esidue. The peptides contain a single conformationally constrained bet a-amino acid residue, while the pseudopeptides also contain a urea lin kage and two peptide chains running in parallel directions. The key st ep in the synthesis is a Curtius rearrangement on the amido acids 6a,b to generate an isocyanate that is then directly reacted with suitably protected amino acids and peptides to give the peptides and pseudopep tides. The synthesis of the peptide analogue 4 is also described; in t his compound, the two peptide chains run parallel to one another, and the stereochemistry of the norbornene unit within compound 4 was deter mined by X-ray analysis of the related peptide analogue 23.