Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, USA.
J Nat Prod. 2010 Mar 26;73(3):365-72. doi: 10.1021/np9005986.
The focus of this study is on the bastadin class of bromotyrosine derivatives, commonly isolated from Ianthella marine sponges, and is the first report on the secondary metabolites from Ianthella cf. reticulata. Two new bastadins were isolated, (E,Z)-bastadin 19 (1a), a diastereoisomer of the known (E,E)-bastadin 19 (1b), and dioxepine bastadin 3 (2), an unusual dibenzo-1,3-dioxepine. A bastadin NMR database was created and assisted in the structure determination of 1b and 2 and the rapid dereplication of 10 other known compounds including bastadins 2-9 (3-10), 13 (11), and 19 (1a). The geometry of the 2-(hydroxyimino)-N-alkylamide chains, a chemical feature present in all bastadins, was further probed, and new insights regarding the natural oxime configuration are discussed. Bastadins possessing (E,Z)-, (Z,E)-, or (E,E)-dioxime configurations could be artifacts of isolation or storage in solution. Therefore, this point was explored by photochemical and thermal isomerization studies, as well as molecular mechanics calculations. Bastadins 13 (11) and 19 (1a) exhibited moderate inhibition against Trypanosoma brucei, and bastadin 4 (5) was cytotoxic to HCT-116 colon cancer cells.
本研究的重点是溴酪氨酸衍生的巴斯塔丁类化合物，这类化合物通常从海洋海绵 Ianthella 中分离得到，这也是首次报道来自 Ianthella cf. reticulata 的次级代谢产物。本研究从该海绵中分离得到了两种新的巴斯塔丁类化合物，(E,Z)-巴斯塔丁 19（1a），一种已知的(E,E)-巴斯塔丁 19（1b）的非对映异构体，以及二氧杂环戊烯巴斯塔丁 3（2），一种不常见的二苯并-1,3-二氧杂环戊烯。本研究创建了一个巴斯塔丁 NMR 数据库，用于协助确定 1b 和 2 的结构，以及对 10 种其他已知化合物（包括巴斯塔丁 2-9（3-10）、13（11）和 19（1a））的快速鉴定。对所有巴斯塔丁都存在的 2-（羟亚氨基）-N-烷基酰胺链的几何形状进行了进一步研究，并讨论了关于天然肟构型的新见解。具有(E,Z)-、(Z,E)-或(E,E)-肟构型的巴斯塔丁可能是分离或在溶液中储存的人为产物。因此，通过光化学和热异构化研究以及分子力学计算来探讨了这一点。巴斯塔丁 13（11）和 19（1a）对 Trypanosoma brucei 表现出中等抑制作用，而巴斯塔丁 4（5）对 HCT-116 结肠癌细胞具有细胞毒性。
