Kinetic control of proline amide rotamers: total synthesis of trans,trans- and cis,cis-ceratospongamide.

Ceratospongamide is a cyclic peptide natural product that is biosynthesized as a mixture of two proline rotamers. Remarkably, these rotamers do not detectably interconvert at temperatures up to 100 degress C. Here we report high-yielding syntheses of each rotamer and demonstrate that the threonine-derived oxazoline plays a critical role in determining the kinetic distribution of conformational isomers.