Synthesis of (+/-) mappicine and mappicine ketone

Mappicine and mappicine ketone are camptothecin analogs of interest as antiviral agents. A novel synthesis of these compounds is described using a Friedlander condensation. The requisite ketone is prepared via a regioselective ortho-directed metallation/alkylation of a trisubstituted pyridine. This is condensed with N-t-butyloxycarbonyl-o-aminobenzaldehyde as a convenient, stable o-aminobenzaldehyde equivalent in the Friedlander condensation.