Synthesis Of Winolide A To Determine The Absolute Configuration And Activity Research Of Its Derivatives

Sesquiterpenes are an important class of natural products found generally in naturewhich displayed high diverse biological activities, such as anti-inflammatory, antitumor,antiviral, antimicrobial, anticoagulated blood.Wissmanolide A-C were first isolated by our research group, which was a novelEudesman-Sesquiterpene, and following by the preliminary screening, these compoundspresented better anti-inflammatory activity. The subject’s task was to complete the totalsynthesis of demethyl-analogs of Wissmanolide A to certify the absolute configuration of7-C by combining synthesis, X-ray and CD spectrum. At the same time, we try toaccomplish synthesis of Wissmanolide A-C, and set research to aim directly at the keyprocedure―SP2-SP3cross-coupling reaction.With key intermediate SWH-3in hand, we complete the synthesis of16pairs ofderivatives by simple esterification reaction with different substituted phenyl isocyanate.All synthesized derivatives were evaluated for their anti-inflammation and antitumoractivity. The result indicated that almost all of the compounds exhibited strong NOproduction inhibitory effect, compound SWH-4s-2showed significant inhibition on NOproduction and low cytotoxicity simultaneously. To investigate cytotoxicity against threehuman hepatocellular carcinoma cell lines of these derivatives, we choose QGY-7703,HepG-2and SMMC-7721as research object. The result showed that part of compoundsexhibited antitumor activity. Compound SWH-4r-1exhibited strong activity to HepG-2with IC50value0.44μM and good toxicity selectivity. At last, we make simple research of structure-activity relationship.