NMR studies of dimeric and polymeric lactams.

Abstract

The aim of this work was to study the solution conformation of dimeric and polymeric 1actams. In a first part of this work, the synthesis of bicyc1odi1actams as precursors of the polymers was explored. A new preparation for the 2, 5-diazabicyc1o [2,2,2] octa-3, 6-dione was developed. The dimers and polymers were obtained from the N-protected cis- and trans- 3-amino-6-carboxy-2-piperidone for which an improved synthesis was found. Base treatment of the trans activated ester led to the polymer. Using the methods of solution phase peptide synthesis, the four possible dimers were prepared. After transformation to the paranitrophenyl esters, they polymerized to oligomeric species under the same treatment. The solution conformation of the monomeric, dimeric and polymeric species was determined by 1- and 2-dimensional NMR techniques. The 1actam rings have a chair-like conformation in solution. The cis- 1actam is a powerful β-turn- inducer when incorporated in synthetic peptides. The cis- lactam was found, however, to have a very similar conformation in DMSO solution, without hydrogen bonding to stabilize the turn. No evidence was found for the β-turn in the dimers and polymers using 2-dimensional NMR techniques. The dimers were found to exist in an extended conformation in DMSO. The fact that every other amide bond is in the cis configuration, as well as the steric crowding due to the rings may not allow the existence of the β-turn.