A Convergent Total Synthesis of the Telomerase Inhibitor (±)-γ-Rubroinycin

摘要

The total synthesis of the human telomerase inhibitor y-rubromycin in its racemic form was accomplished in 3.8% overall yield. The key feature of this synthesis is an efficient acid-catalyzed spiroketalization for the construction of the spiroketal core. The required electronically well-balanced spiroketal precursor was obtained by the convergent assembly of a naphthyl-substituted aldehyde, an a-melhoxy-allyl-y-silyl-substituted phosphonate as the central C., building block, and a highly functionalized aryl Grignard reagent. Another key feature is the late-stage construction of the isocoumarin moiety and a simultaneous protodesilylalion furnishing the known methyl aryl ether protected precursor of y-rubromycin.