Syntheses and Cytotoxicity of the AB-, C-, and BC-Ring Systems of Sesbanimides

Preparation of some AB-ring systems 5 and 8 of sesbanimides 1 and 2, potent antitumor alkaloids, were performed starting from the synthetic intermediates of our first total synthesis of 1 and 2. The C-ring systems 14a–d were synthesized by applying the previously explored novel Reformatsky reaction to various aldehydes. The optically active BC-ring systems 20 and 21 having the same absolute configurations as those of 1 and 2, were derived from (−)-2,4-O-methylene D-sorbitol (15) as the B-ring synthon. Since all of these compounds 5, 8, 14a–d, 20, and 21 and the previously synthesized AB-ring system 3 showed no significant in vitro cytotoxicity against P388 murine leukemia, its appeared evident that 1 and 2 exhibit their notable antitumor activity owing to cooperation of the A- and C-rings.

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