Asymmetric Synthesis of (+)- and (-)-Wuweizisu C Stereoisomers and Their Chemosensitizing Effects on Multidrug-Resistant Cancer Cells

Abstract

Total syntheses of the dibenzocyclooctadiene natural product wuweizisu C in its (-)-form [(S)-1] and its (+)-form [(R)-1] were achieved in 19 steps, starting from commercially available gallic acid. In the key step, the asymmetric biphenyl axis was constructed by an oxazoline-mediated Ullmann reaction to provide either the P or M biaryl product in 68% yield and >99% de, depending on the configuration of the oxazoline. The efficiency of this total synthesis was excellent, as the syntheses of (S)-1 and (R)-1 from intermediate 7 each proceeded in 13 steps with an overall yield of 6.8%. (S)-1 and (R)-1 were evaluated as chemosensitizers for multidrug-resistant cancers.