Novel alpha,alpha-disubstituted alpha-aminoacids with axial dissymmetry and their N- or C-protected derivatives

Racemic as well as enantiomerically pure 1,1'-binaphthyl-substituted alpha-aminoisobutyric acid (Bin), a new chiral atropoisomeric alpha, alpha-disubstituted glycine, and its biphenyl analogue (Bip), have been prepared with good yields by bis-alkylation of a glycine tert-butyl ester Schiff base with 2,2'-bis(bromomethyl)-1, 1'-binaphthyl and 2,2'-bis(bromomethyl)-1,1'-biphenyl, respectively, under phase transfer conditions. The free aminoacids Bin and Bip, as well as their N-protected (Z, Boc, Fmoc) and/or C-protected (ethyl or tert-butyl esters) derivatives, useful for the incorporation of these new aminoacids into peptides, have been obtained. A slow interconversion between the two enantiomers of the Bip derivatives is generally observed in H-1 NMR at room temperature, with a rotational energy barrier of 59 kJ mol(-1). (C) 1997 Elsevier Science Ltd.