Synthesis of 4,4-disubstituted 2-aminocyclopentanecarboxylic acid derivatives and their incorporation into 12-helical β-peptides

(Chemical equation presented) An enantioselective synthetic route is reported for trans-2-aminocyclopentanecarboxylic acids (ACPC) bearing geminal side chain pairs at the 4-position. β-Peptides containing the 4,4-disubstituted ACPC residues adopt the 12-helical conformation, as demonstrated by 2D NMR analysis in aqueous solution. These 4,4-disubstituted ACPC residues display functional groups, including acidic and hydrogen bond donating groups, in a geometrically defined fashion, which should be useful for the design of β-peptides for specific applications.