Polyhydroxylated cyclopentane β-amino acids derived from D-mannose and D-galactose: synthesis and protocol for incorporation into peptides

A stereoselective synthesis of polyhydroxylated cyclopentane β-amino acids from hexoses is reported. The reaction sequence comprises as key steps a Ring Closing Metathesis of a polysubstituted diene intermediate, followed by the stereoselective aza-Michael functionalization of the resulting cyclopent-1- ene-1-carboxylic acid ester. Examples of synthesis of polysubstituted 2-aminocyclopentanecarboxylic acid derivatives starting from protected D-mannose and D-glucose are presented. A general protocol for the incorporation of these highly functionalized alicyclic β-amino acids into peptides is also reported.