synthesis of the marine pyrroloiminoquinone alkaloids, discorhabdins海洋pyrroloiminoquinone生物碱的合成,discorhabdins.pdf

Mar. Drugs 2010, 8, 1394-1416; doi:10.3390/md8041394 OPEN ACCESS Marine Drugs ISSN 1660-3397 /journal/marinedrugs Review Synthesis of the Marine Pyrroloiminoquinone Alkaloids, Discorhabdins Yasufumi Wada 1,†, Hiromichi Fujioka 1,* and Yasuyuki Kita 1,2,* 1 Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka, 565-0871, Japan 2 College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga, 525-8577, Japan † JSPS Research Fellow. * Authors to whom correspondence should be addressed; E-Mails: fujioka@phs.osaka-u.ac.jp (H.F.); kita@ph.ritsumei.ac.jp (Y.K.); Tel.: +81 6 6879 8225; Fax: +81 6 6879 8229. Received : 7 April 2010; in revised form: 16 April 2010 / Accepted: 19 April 2010 / Published: 21 April 2010 Abstract: Many natural products with biologically interesting structures have been isolated from marine animals and plants such as sponges, corals, worms, etc. Some of them are discorhabdin alkaloids. The discorhabdin alkaloids (discorhabdin A-X), isolated from marine sponges, have a unique structure with azacarbocyclic spirocyclohexanone and pyrroloiminoquinone units. Due to their prominent potent antitumor activity, discorhabdins have attracted considerable attention. Many studies have been reported toward the synthesis of discorhabdins. We have accomplished the first total synthesis of discorhabdin A (1), having the strongest activity in vitro among discorhabdins in 2003. In 2009, we have also