Total synthesis of dolastatin 10 through ruthenium-catalyzed asymmetric hydrogenations

Abstract

A total synthesis of dolastatin 10, a potent inhibitor of microtubule assembly, which displayed remarkable antineoplastic activity, is reported. Our synthetic approach was based upon ruthenium-promoted asymmetric hydrogenation of β-keto esters derived from ( S)-Boc-proline and ( S)-Boc-isoleucine for the construction of the two key units: (2 R,3 R)-Boc-dolaproine (Dap) and (3 R)-Boc-dolaisoleucine (Dil).