Synthesis of Phenanthroindolizidine Alkaloids with an Acyloxy Group at the C3 Position and their Antitumor Activities and Toxicities

We previously reported that the phenanthroindolizidine alkaloid 3 and its derivatives had markedly potent in vitro cytotoxicity. However, they had low in vivo antitumor activities and high in vivo toxicities, which was a serious problem for further development. Based on the finding that antitumor activity and toxicity could be improved by acetylation of 3, we synthesized new derivatives of 3, which possessed various acyl groups, and evaluated their antitumor activities and toxicities. We found that derivatives with sterically less bulky acyl groups had improved antitumor activities.