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

The (4<i>R</i>)-hydroxylated analogues of annonaceous acetogenin mimicking compound <b>2</b> 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 IC<sub>50</sub> values of <b>2</b> were 1.6 × 10<sup>-3</sup> and 8 × 10<sup>-2</sup> μg/mL against HT-29 and HCT-8, respectively. A remarkable enhancement effect was observed by the activity comparison of <b>1c</b> and its (4<i>R</i>)-hydroxylated analogue <b>2</b>.