Synthesis of a val-pro diaminodiol dipeptide isostere by epoxyamine cyclization

[GRAPHICS] The stereoselective synthesis of a novel proline-containing dipeptide isostere is described. Starting from L-valine, three new contiguous stereocenters are generated by asymmetric induction and epoxide chemistry, while the pyrrolidine ring of proline is introduced in the final step via intramolecular ring opening of the amino acid derived epoxyamine. Proline-containing peptidomimetics are potentially attractive as selective inhibitors of proline-specific enzymes, such as PPlases and retroviral proteases, and as analogues of bloactive peptides.