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

摘要

Total syntheses of the dibenzocyclooctadiene natural product wuweizisu C in its (-)-form [(S)-1] and its (+)-form [(R)-l] 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)-l and (R)-l from intermediate 7 each proceeded in 13 steps with an overall yield of 6.8%. (S)-l and (R)-l were evaluated as chemosensitizers for mul-tidrag-resistant cancers.