Synthesis of tetrazole analogs of γ- and δ-amino acids

Abstract

N-benzyloxycarbonyl-protected α- or β-amino alcohols, easily prepared from α- and β-amino acids, were converted into aldehydes and directly reacted with (triphenyl phosphoranylidene) acetonitrile, leading to unsaturated nitriles. Treatment of nitriles with NaN3 and ZnBr2 produced unsaturated γ- and δ-amino tetrazoles, which were deprotected and converted to the corresponding saturated compounds by catalytic hydrogenation. For the case of δ-amino tetrazole, the methylation of the acidic moiety occurred after treatment with CH2N2, leading to the N1- and N2-methylated constitutional isomers, which were separated by column chromatography and hydrogenated. Copyright © 2006 European Peptide Society and John Wiley & Sons, Ltd