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 sy nthesized by alpha,alpha-bis-alkylation of alkyl cyanoacetates with 2,2'-bi s-(bromomethyl)-1,1'-diphenyl, followed by NaBH4/CoCl2 reduction of the cya no group. Both its C- and N-protected derivatives have been obtained. A slo w interconversion at the NMR time scale is generally observed between the t wo enantiomers of the conformationally labile beta(2,2)-HBip residue. The h omo-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 conform ational analysis has been performed by H-1 NMR and FT-IR absorption techniq ues. (C) 2000 Elsevier Science Ltd. All rights reserved.