β-Homo-peptides Built from β2,2-HBip, a Biphenyl-substituted 3-Amino-2,2-dimethylpropanoic Acid

A novel β2,2-gem-disubstituted amino acid, β2,2-HBip, has been synthesized by α,α-bis-alkylation of alkyl cyanoacetates with 2,2′-bis-(bromomethyl)-1,1′-diphenyl, followed by NaBH4/CoCl2 reduction of the cyano group. Both its C- and N-protected derivatives have been obtained. A slow interconversion at the NMR time scale is generally observed between the two enantiomers of the conformationally labile β2,2-HBip residue. The homo-peptides Boc-(β2,2-HBip)n-OMe have been prepared in solution by the EDC/HOBt coupling method to the hexamer level and a preliminary conformational analysis has been performed by 1H NMR and FT-IR absorption techniques.