Studies On The Total Synthesis Of (+)- And (-)-Wuweizisu C And Biological Activity

Lignans are an important series of natural products. A variety of lignans classes have been isolated from different plants, whose carbon skeletons are constructed by the linking of two phenyl propane unit. The results of pharmacology show these compounds possess a wide variety of biological activity. These compounds have long been recognized as challenging targets for organic synthesis due to the special structure and the important biological properties exhibited by some members of this class.Wuweizisu C is considered as a crucial component for the antihepatotoxic and anti-HIV activity found in traditional Chinese medicine formulations of Wuweizi lignan containing plants. It is difficult to obtain large amount of lignans by abstraction of plants, because the natural Wuweizisu C is only 0.08%. So, it is essential to chiral synthesis of Wuweizisu C. Although there have been five successful route to the synthesis of Wuweizisu C, they are syntheses of racemic Wuweizisu C. The paper designed and synthesized the chiral Wuweizisu C.The total synthesis of dibenzocyclooctadiene natural product (-)-Wuweizisu C and (+)-Wuweizisu C have been achieved for the first time in 19 steps starting from commercially available gallic acid in 1.54% yield and 96% de. The key step, oxazoline-mediated Ullmann reaction, provided the biaryl products in 68% yield and 99% de. In this step, the Ullmann reaction of the S-oxazoline gave Pax-biphenyl compound, and the R-oxazoline gave Max-biphenyl compound. And the other key step– cyclization– was obtained by intramolecular nucleophilic substitution reaction. (+)- and (-)-Wuweizisu C can be obtained following a series of reaction. The structure of these products have been identified by 1HNMR,13CNMR,HRMS spectra.In the paper, the enantiomeric biphenyl compounds prepared were separated for the first by using chiral HPLC. The ee and de of biphenyl compounds were received by this way. The absolute configuration of biphenyl bond was confirmed by the Cotton effect according to the CD (Circular Dichroism) rule. The mould of biphenyl compounds (non-bridged biphenyl compounds and bridging-bond compounds) was established. Finaly, the X-ray crystal structure of (+)-Wuweizisu C and (-)-Wuweizisu C were received to confirmed their absolutely configuration.From the pharmacology results, it was confirmed that the (-)-Wuweizisu C could significantly decrease the elevation of sGPT(serum Glutamic Pyruvic Transaminase) levels induced by CCl4 and the activities of (-)-Wuweizisu C was stronger than its R enantiomer.