A synthetic and computational investigation of pentacycloundecane amino acid derivatives.

Abstract

Computational studies have shown that cage skeletons (7) have the tendency to impose a 310-helix as well as an áL-helix on the polypepeptide chain. Residues such as 7 are the useful tools for study of the conformational preferences of peptide models, the design of peptide analogues with improved pharmacokinetics profiles and the development of pharmacophore models. Synthesis of pentacycloundecane amino acid analogue suitable for peptide synthesis would enable us to verify the computational predictions and to contribute to this very active field of research. The sterically hindered 8-amino-pentacyclo[5.4.0.02,6.03,10.05,9]undecane-8-carboxylic acid (7) was synthesised by hydrolysis of the novel bis-Boc protected pentacycloundecane-hydantoin (30). Progress to incorporate 7 into a non-natural peptides is reported. A computational investigation on the regioselective acetylation of hydantoin derivatives which includes PCU hydantoin, 5.5-dimethylhydantoin and 5-methylhydantoin is also reported. The results of the computational investigation initiated the regioselective synthesis of the mono-Boc and bis-Boc derivatives of 5,5-dimethylhydantoin and 5-methylhydantoin. These compounds have not been reported before.