Synthesis of the four stereoisomers of 4-aminoadamantane-2-carboxylic acid, rigid analogues of γ-aminobutyric acid

Abstract

Synthetic routes to the four stereoisomers of 4-aminoadamantane-2-carboxylic acid are described. π Route cyclisations to 2,4-disubstituted adamantanes are expanded to obtain 4_eq- and 4_ax-acetamidoadamantan-2-ones. These are converted into acetamido-nitriles using tosylmethyl isocyanide and subsequently hydrolysed to three of the amino-acids. The diaxial isomer is prepared by a stereospecific nitrene insertion reaction. Mass spectra of the amino-acids and their ethyl esters are reported.