Synthetic approaches to homocamptothecin antitumor agents

Homocamptothecins are proving to be an especially interesting class of anti-cancer agents because they resemble standard camptothecins in cytotoxicity but have very different pharmacodyanamic properties. This review summarizes synthetic approaches to the parent homocamptothecin and its analogs. Three powerful and general routes—the Lavergne–Comins route, the cascade radical annulation route, and the Friedlander route—have been put into place to make homocamptothecins. These routes are compared and contrasted. Together, they have driven the SAR, preclinical, and clinical development of this class of anti-cancer agents.