Total Synthesis of 34‐Hydroxyasimicin and Its Photoactive Derivative for Affinity Labeling of the Mitochondrial Complex I

The asymmetric total synthe- sis of the 34-hydroxyasimicin and its 3- (4-benzoylphenyl)propionate ester was achieved by means of a convergent synthetic strategy. This ester, which contains eight asymmetric centers, rep- resents the first photoaffinity-labeling agent that is derived from an Annona- ceous acetogenin. The key transforma- tions in the synthesis include the Sharpless asymmetric dihydroxylation reaction, the Wittigolefination reac- tion, an oxidative cyclization reaction with rhenium(vii) oxide, the William- son etherification reaction, and a palla- dium-catalyzed cross-couplingreaction. Use of the target molecule for photoaf- finity-labelingstudies of bovine mito- chondrial NADH-ubiquinone oxidore- ductase (Complex I) may shed light on the structure/function of this intricate enzyme and on the origin of the high antitumor activity exhibited by the An- nonaceous acetogenins.