NOVEL ALPHA,ALPHA-DISUBSTITUTED ALPHA-AMINO-ACIDS WITH AXIAL DISSYMMETRY AND THEIR N-PROTECTED OR C-PROTECTED DERIVATIVES

Racemic as well as enantiomerically pure 1,1'-binaphthyl-substituted a lpha-aminoisobutyric acid (Bin), a new chiral atropoisomeric alpha, al pha-disubstituted glycine, and its biphenyl analogue (Bip), have been prepared with good yields by bis-alkylation of a glycine tert-butyl es ter Schiff base with 2,2'-bis(bromomethyl)-1, 1'-binaphthyl and 2,2'-b is(bromomethyl)-1,1'-biphenyl, respectively, under phase transfer cond itions. The free aminoacids Bin and Bip, as well as their N-protected (Z, Boc, Fmoc) and/or C-protected (ethyl or tert-butyl esters) derivat ives, useful for the incorporation of these new aminoacids into peptid es, have been obtained. A slow interconversion between the two enantio mers of the Bip derivatives is generally observed in H-1 NMR at room t emperature, with a rotational energy barrier of 59 kJ mol(-1). (C) 199 7 Elsevier Science Ltd.