Matsuzawa Masayoshi, Kakeya Hideaki, Yamaguchi Junichiro, Shoji Mitsuru, Onose Rie, Osada Hiroyuki, Hayashi Yujiro
Department of Industrial Chemistry, Faculty of Engineering, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan.
Chem Asian J. 2006 Dec 18;1(6):845-51. doi: 10.1002/asia.200600199.
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.
