beta-Homo-peptides built from beta-2,2-HBip, a biphenyl-substituted 3-amino-2,2-dimethylpropanoic acid

A novel beta(2,2)-gem-disubstituted amino acid, beta(2,2)-HBip, has been synthesized by alpha,alpha-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 beta(2,2)-HBip residue. The homo-peptides Boc-(beta(2,2)-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 H-1 NMR and FT-IR absorption techniques.