Enantio- and diastereoselective total synthesis of (+)-panepophenanthrin, a ubiquitin-activating enzyme inhibitor, and biological properties of its new derivatives.
The asymmetric total synthesis of (+)-panepophenanthrin, an inhibitor of ubiquitin-activating enzyme (E1), has been accomplished using catalytic asymmetric alpha aminoxylation of 1,4-cyclohexanedione monoethylene ketal as a key step, followed by several diastereoselective reactions. The biomimetic Diels-Alder reaction of a monomer precursor was found to proceed efficiently in water. The investigation of the biological properties of new derivatives of (+)-panepophenanthrin enabled us to develop new cell-permeable E1 inhibitors, RKTS-80, -81, and -82.
Matsuzawa
Masayoshi
M
Department of Industrial Chemistry, Faculty of Engineering, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan.
Kakeya
Hideaki
H
Yamaguchi
Junichiro
J
Shoji
Mitsuru
M
Onose
Rie
R
Osada
Hiroyuki
H
Hayashi
Yujiro
Y
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D010616:Phenanthrenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D044764:Ubiquitin-Activating Enzymes / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D010616:Phenanthrenes; C468593:panepophenanthrin; D044764:Ubiquitin-Activating Enzymes