Asymmetric synthesis of phenanthroindolizidine alkaloids with hydroxyl group at the C14 position and evaluation of their antitumor activities.
The asymmetric total synthesis of the strongly cytotoxic phenanthroindolizidine alkaloid 3 was achieved. Using the same route, various derivatives were also synthesized. Cytotoxicity of those synthetic compounds was evaluated and compounds 19, 23, and 27 demonstrated potent cytotoxicities similar to that of 3. The in vivo antitumor efficacy of selected compounds was also evaluated and 23 demonstrated moderate antitumor efficacy.
Yakult Central Institute for Microbiological Research, 1796 Yaho, Kunitachi-shi, Tokyo 186-8650, Japan. takashi-ikeda@yakult.co.jp
Takashi
T
Ikeda
Takashi
T
Yaegashi
Takeshi
T
Matsuzaki
Syusuke
S
Hashimoto
Seigo
S
Sawada
D000470:Alkaloids / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D054836:Indolizidines / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D007212:Indolizines / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy; D010618:Phenanthrolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D013329:Structure-Activity Relationship
D000470:Alkaloids; D000970:Antineoplastic Agents; D054836:Indolizidines; D007212:Indolizines; D010618:Phenanthrolines; C521640:phenanthroindolizidine