Asymmetric total synthesis and stereochemical elucidation of the antitumor agent PM-94128

[reaction: see text]. PM-94128, a novel depsipeptide antitumor agent, has been synthesized for the first time through a highly stereocontrolled route. The key steps for the synthesis of the dihydroxyamino acid moiety involve a diastereoselective addition of tert-butyl lithiopropiolate to a chiral nitrone and a 2,3-dihydro[1,2]oxazin-6-one dihydroxylation. The synthesis serves to define the relative as well as the absolute configuration of the natural product (bearing five stereogenic centers).