Synthesis of pyrrolizidine alkaloids indicine, intermedine, lycopsamine, and analogues and their N-oxides. Potential antitumor agents.
(-)- and (+)-trachelanthic and (-)- and (+)-viridifloric acids were synthesized and their isopropylidene derivatives were regiospecifically coupled, at C-9, with (-)-retronecine obtained by hydrolysis of monocrotaline, isolated from Crotalaria spectabilis. Hydrolysis, followed by oxidation, led to the N-oxides of indicine, intermedine, lycopsamine, and the new nonnatural product, respectively. Each of these analogues was screened in the P388 lymphocytic leukemia system at the same time as indicine N-oxide, and the results were compared. Other related analogues were prepared and similarly screened and the results compared with those from indicine N-oxide.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D007941:Leukemia P388 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D011763:Pyrrolizidine Alkaloids / Q000138:chemical synthesis* / Q000494:pharmacology
D000970:Antineoplastic Agents; D011763:Pyrrolizidine Alkaloids; C013095:indicine-N-oxide; C018336:indicine