Total synthesis of 34-hydroxyasimicin and its photoactive derivative for affinity labeling of the mitochondrial complex I.
The asymmetric total synthesis 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, represents the first photoaffinity-labeling agent that is derived from an Annonaceous acetogenin. The key transformations in the synthesis include the Sharpless asymmetric dihydroxylation reaction, the Wittig olefination reaction, an oxidative cyclization reaction with rhenium(vii) oxide, the Williamson etherification reaction, and a palladium-catalyzed cross-coupling reaction. Use of the target molecule for photoaffinity-labeling studies of bovine mitochondrial NADH-ubiquinone oxidoreductase (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 Annonaceous acetogenins.
Han
Hongna
H
Department of Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA. hanhn@scripps.edu
Sinha
Mantosh K
MK
D'Souza
Lawrence J
LJ
Keinan
Ehud
E
Sinha
Subhash C
SC
D000818:Animals; D002417:Cattle; D042967:Electron Transport Complex I / Q000032:analysis*; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry; D008929:Mitochondria, Heart / Q000201:enzymology*; D015394:Molecular Structure; D019920:Photoaffinity Labels / Q000138:chemical synthesis / Q000737:chemistry*
C492877:34-hydroxyasimicin; D005663:Furans; D019920:Photoaffinity Labels; D042967:Electron Transport Complex I