Enantioselective Synthesis of Neocarzinostatin Chromophore Aglycone

An enantioselective synthesis of neocarzinostatin chromophore aglycone (6) is described. The key features of the synthesis include 1) Sharpless asymmetric epoxidation of the allylic alcohol 136 to produce epoxy alcohol 137, 2) an intramolecular acetylide addition within the epoxy aldehyde 138 to furnish alcohol 139, 3) esterification of the diol 171 with the acid 22 and in situ cleavage of the chloroacetate ester to provide ester 172, 4) elimination of the C-1 alcohol of 175 to afford the olefin 176, and 5) reductive opening of epoxy alcohol 120 with the combination of iodine, triphenylphosphine, and imidazole to afford neocarzinostatin chromophore aglycone (6). The synthetic pathway described is highly convergent, and should the supply quantities of 6 necessary for ongoing studies directed toward the completion of the total synthesis of neocarzinostatin chromophore (1), as well as the preparation of analogs bearing modified sugar residues.