Formal Synthesis of Diflomotecan

Significance

Camptothecin is an alkaloid from the Chinese tree Camptotheca accuminata with potent topisomerase I activity. The lactone ring easily hydrolyses in neutral media to a nearly inactive carboxylate. Diflomotecan has greater hydrolytic stability. Two asymmetric syntheses of diflomotecan are reported, both based on an Evans acetate aldol reaction. The more efficient second route to the fragment I (9 steps, 11.1% overall) involving a single chromatography is shown here. The good dr in the acetate aldol reactions using lithium enolates is noteworthy.