Studies aimed at the total synthesis of the antitumor antibiotic cochleamycin A. An enantioselective biosynthesis-based pathway to the AB bicyclic core.

[reaction: see text] A convergent, highly enantioselective synthesis of the fully functionalized AB sector of cochleamycin A is described. A pair of building blocks, crafted from L-malic and L-ascorbic acids, are conjoined in a manner that gives rise to an (E,Z,E)-1,6,8-nonatriene. On heating, the latter undergoes stereocontrolled intramolecular Diels-Alder cyclization via an endo transition state.