Biosynthesis inspired asymmetric total synthesis of camptothecin

An asymmetric total synthesis of camptothecin taking advantage of a biosynthetic skeletal transformation is described. The synthesis features an improved one-pot Mannich/acylation/Wittig reaction enabled by a newly developed <i>N</i>-sulfonylated amide catalyst, intramolecular [4+2] cycloaddition, a highly diastereoselective dihydroxylation, and a late-stage scaffold transformation from a monoterpene indole to give a quinoline framework <i>via</i> a Winterfeldt oxidation. These key steps collectively enable a concise and enantioselective synthesis of the antitumor agent (20<i>S</i>)-camptothecin.