Norbornyl Dipeptide Analogues: Mimics of Both a Transition State and a Torsionally Distorted Ground State

The 1-amino-2-hydroxybicyclo[2.2.1]heptane-7-carboxylic acid derivatives 1-3 have been synthesized, the pivotal step being the use of an acyl nitrene-insertion reaction to introduce nitrogen functionality into the corresponding hydroxy ester. The analogues each mimic a distorted peptide ground state as well as the transition state for peptide bond hydrolysis. To enhance the immune response and to provide further sequence specificity, the analogues 1-3 have been coupled to at least one D-amino acid residue to yield the derivatives 21, 26, and 27, respectively. Antibodies elicited against these derivatives may catalyze the hydrolysis of the corresponding peptides both by straining the substrate ground state and by stabilizing the transition state.