Design, synthesis, and evaluation of novel kazusamycin A derivatives as potent antitumor agents

Novel kazusamycin A derivatives were designed in the viewpoint of decrease of reactivity at the α,β-unsaturated δ-lactone moiety against Michael-type addition. Although 25–30 steps were required for the synthesis of each compound, their syntheses were achieved. Cytotoxicity against HPAC cell line was evaluated, and two of them exhibited comparable potency to kazusamycin A. Hepatic toxicity of these designed compounds was much lower than that of kazusamycin A.