Synthesis and conformational studies of peptidomimetics containing a carbocyclic 1,3-diacid

A rigid carbocyclic scaffold comprising of an all-cis 4,5-dihydroxy-1,3-cyclopentanedicarboxylic acid is developed. Attachment of peptide strands to the carboxylic groups of this novel template led to the peptidomimetics 2 and 3. Conformational analysis by circular dichroism and NMR studies revealed that these molecules adopt a unique folded structure in nonpolar solvent involving intramolecular hydrogen bonding between PheNH of one strand and LeuCO (in 2) or GlyCO (in 3) of the other strand. This structure is very different from the structures observed earlier in their sugar counterparts (1). The paper describes in detail the synthesis and structural studies of compounds 2 and 3.