Enantioselective Synthesis of Kedarcidin Chromophore Aglycon in Differentially Protected Form

Four components, each prepared in multigram amounts, have been assembled in the convergent (25 steps in the longest linear sequence), enantioselective synthesis of the differentially protected kedarcidin chromophore aglycon (1). In addition to the enantioselective synthesis of each of the four components, the route features a transannular anionic cyclization to form the bicyclo[7.3.0]dodecadienediyne core in the presence of an ansa-bridged macrolactone. MOM=methoxymethyl, TIPS=triisopropylsilyl, TES=triethylsilyl.