Studies on the syntheses of heterocyclic compounds. Part 878. Synthesis of (±)-camptothecin and (±)-10-methoxycamptothecin via enamine annulation

Abstract
Synthesis of (±)-camptothecin (1) and (±)-10-methoxycamptothecin (2) was achieved via enamine annelation as a key step. Condensation of 3,4-dihydro-1-methyl-β-carbolines (9) and (10) with unsaturated tetra-esters (6) and (7) followed by reduction gave the indolo[a]quinolizin-4-ones (12) and (13). Photo-oxygenation of (12) and (13) and subsequent base treatment produced the indolizino[1,2-b]quinolones (16) and (17), which were converted into the pyridones (20) and (24). The former (20) had been correlated to (±)-camptothecin, while the latter (24) was transformed into (±)-10-methoxycamptothecin by application of the established method.