A reasonably stereospecific multistep conversion of Boc-protected α-amino acids to Phth-protected β3-amino acids

A method for the synthesis of β3-amino acids starting from α-amino acids is described. This conversion can be effected by an eight-step procedure which involves the transformation of the carboxylic group into an alkyne followed by a selenium-mediated conversion of the carbon-carbon triple bond to a Se-phenyl selenocarboxylate intermediate. The reactive Se-phenyl selenocarboxylate intermediates can be trapped with water, alcohols or the amine of an amino acid derivative to give β3-amino acids, β3-amino esters or mixed peptides, respectively. The whole transformations of the carboxylic group into an alkyne and of the alkyne group into β3-amino acids may not require purification of the intermediate products but a work-up and isolation procedure of crude materials.

Graphical abstractA selenium-mediated protocol for the homologation of N-Boc α-amino acids into the corresponding N-phthaloyl β-amino acids has been developed.Download full-size image