Synthesis of 18-Noranhydrocamptothecin Analogs Which Retain Topoisomerase I Inhibitory Function

Article abstract of DOI:10.1021/jo00102a030

The total syntheses of compounds 2 and 3 are described.Key departures from previous routes to camptothecin from these laboratories involved (i) early incorporation of C2 oxygen (see compound 9) and (ii) recourse to a Heck vinylation for installation of a hydroxymethyl equivalent on the pyridone (see transformation 15 -> 16).The final compounds are of considerable interest in that they are the most drastically modified E ring systems which retain topoisomerase I inhibitory function.