Novel syntheses of camptothecin alkaloids. Part 2. Concise synthesis of (S)-camptothecins

Article abstract of DOI:10.1016/0040-4039(96)01205-1

A 9-step, convergent total synthesis of (S)-camptothecin alkaloids is described. The intramolecular [4 + 2] cycloaddition of an N-arylimidate with an alkyne is used to prepare the alkaloid ABC ring system. The chiral center is derived utilizing Seebach's chemistry for the diastereoselective Michael addition of a chiral dioxolanone enolate to a methylene malonate acceptor. The total synthesis of non-racemic topotecan is accomplished from (S)-10-hydroxycamptothecin in an additional step.