P-44 多環性海洋天然物ラメラリンDを先導物質とする新規トポイソメラーゼI阻害剤の設計と合成(ポスター発表の部)
スポンサーリンク
概要
- 論文の詳細を見る
Lamellarin-class natural products have attracted considerable attention due to their unique structure and highly useful biological activities. For example, lamellarin D (1) exhibits potent cytotoxicity on P-glycoprotein-mediated multidrug-resistant (MDR) cancer cells. In 1997, we have reported the first total synthesis of 1 using N-ylide-mediated cyclization of a benzylisoquinoline derivative as the key ring-construction procedure. By using this strategy, we have synthesized ten lamellarin D analogues and carried out a structure-activity relationship (SAR) study. In this study, we revealed that the hydroxyl group at C-8 and C-20 positions are essential for cytotoxic activity. Recently, Bailly et al. have reported 1 is a potent inhibitor of DNA topoisomerase I and presented a theoretical model of 1-DNA-topoisomerase I ternary complex. The model is in perfect agreement with our SAR study. Based on these previous studies, we designed 1-dearyllamellarin D (2) and its C-1 substituted derivatives 3 as novel antitumor compounds. The synthesis of 2 has been achieved by combinational use of regioselective lithiation, Suzuki-Miyaura coupling, Mitsunobu type reaction, and intramolecular Heck reaction as key reactions. Electrophilic substitution of 22 proceeded at 1-position selectively to afford 23. In addition, bromide 23c could be converted into C-1 arylated or methylated 24 by using Pd-catalyzed Suzuki-Miyaura coupling reaction. These reactions allowed to produce a number of C-1 substituted 3.
- 天然有機化合物討論会の論文
- 2008-09-01
著者
関連論文
- P-44 多環性海洋天然物ラメラリンDを先導物質とする新規トポイソメラーゼI阻害剤の設計と合成(ポスター発表の部)
- 位置選択的リチオ化反応を利用したインドール環の効率的官能化
- 98(P18) アゼピノインドール型麦角アルカロイド、クラビシピチン酸の合成(ポスター発表の部)
- 74(P58) 天然有機化合物合成を指向した立体選択的炭素-炭素結合反応の開発(ポスター発表の部)
- カルベノイド反応の新展開 : 新たな不斉合成反応の開発に向けて
- 104(P32) 不斉環拡大反応を鍵反応とする(-)-Isoavenaciolideの触媒的不斉合成(ポスター発表の部)