Enantioselective Synthesis of Neocarzinostatin Chromophore Aglycon

Abstract

Neocarzinostatin is the first of the “enediyne” antitumor agents to be characterized and is further distinguished as the first chromoprotein antibiotic.1 The DNA-cleaving properties of the neocarzinostatin protein-chromophore complex have been shown to reside solely within the chromophore component (1) which, in isolation, is exceedingly unstable.2,3 The strain, structural complexity, and, most importantly, high reactivity of the chromophore core define an extraordinarily challenging synthetic target. In this work, we describe an enantioselective route that provides for the first time neocarzinostatin chromophore aglycon (2), a substance which proves to be even less stable than 1 and which, almost certainly, could not be derived from the parent antibiotic.