A flexible synthetic route to isoxazolidine β-proline analogs

The function and higher order structure of β-proline oligomers have been relatively unexplored compared to other foldamer classes due in part to synthetic challenges associated with substituted monomers. Here we report a flexible synthesis of di- and trisubstituted isoxazolidine β-proline monomers that enables access to a wide range of densely functionalized analogs suitably protected for solid-phase synthetic protocols. This strategy utilizes chiral isoxazolines as key intermediates and can readily provide single stereoisomers of the target molecules.