Mimicry of Annonaceous Acetogenins:  Enantioselective Synthesis of a (4R)-Hydroxy Analogue Having Potent Antitumor Activity

The (4R)-hydroxylated analogues of annonaceous acetogenin mimicking compound 2 were designed and synthesized structurally on the basis of the naturally occurring annonaceous acetogenin bullatacin, which was discovered as a typical member of the novel family of polyketides with potent cytotoxicity, antitumoral, and other biological activities. The preliminary screenings show that the IC₅₀ values of 2 were 1.6 × 10^-3 and 8 × 10^-2 μg/mL against HT-29 and HCT-8, respectively. A remarkable enhancement effect was observed by the activity comparison of 1c and its (4R)-hydroxylated analogue 2.