Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases , National Institutes of Health , Bethesda , Maryland 20892-0820 , United States.
Center for Biomolecular Science and Engineering , Naval Research Laboratory , Code 6930, Washington , D.C. 20375 , United States.
J Am Chem Soc. 2020 Feb 12;142(6):2755-2759. doi: 10.1021/jacs.9b12926. Epub 2020 Jan 30.
Haliclonadiamine and papuamine are bis-indane marine natural products isolated from the marine sponge sp. Their relative structures were previously reported to differ by inversion at only one of their eight shared stereocenters. Here X-ray crystallography shows the opposite to be true: papuamine has a 1,3,8,9,14,15,20,22 configuration, while haliclonadiamine has a 1,3,8,9,14,15,20,22 configuration. Paradoxically the ECD of each structure displays a negative Cotton effect. X-ray crystallography reveals the two structures adopt similar conformations of their 13-membered macrocyclic core that comprises a configurationally relevant diene. B97x-D/Def2-TZVPP-(MeOH)-calculated ECD supports the diene configuration with the macrocycle dominating the ECD Cotton effect for haliclonadiamine and papuamine. Additional crystallographic and chiroptical analyses of three sponge samples from geographically distant locations indicate this pair of natural products always exists as a configurationally related couple. The co-discovery of a biosynthetic precursor, halichondriamine C, present in these same Haliclona samples must be considered when discussing any biosynthetic pathway. Taken together, this work justifies a reassignment of haliclonadiamine's structure and opens the question of how this complex stereochemical relationship between haliclonadiamine and palauamine arises biosynthetically.
海拉克林二胺和巴布胺是从海洋海绵 sp 中分离得到的双茚烷海洋天然产物。它们的相对结构以前被报道仅在其八个共享的立体中心之一处发生反转。这里的 X 射线晶体学表明事实正好相反：巴布胺具有 1,3,8,9,14,15,20,22 构型，而海拉克林二胺具有 1,3,8,9,14,15,20,22 构型。矛盾的是，每个结构的 ECD 都显示出负的 Cotton 效应。X 射线晶体学揭示了这两个结构采用了相似的 13 元大环核心构象，其中包含一个构型相关的二烯。B97x-D/Def2-TZVPP-(MeOH)-计算的 ECD 支持二烯的构型，大环对海拉克林二胺和巴布胺的 ECD Cotton 效应起主导作用。对来自地理位置遥远的三个海绵样本的额外晶体学和手性分析表明，这对天然产物总是作为构型相关的一对存在。在讨论任何生物合成途径时，都必须考虑到在这些相同的 Haliclona 样本中存在的生物合成前体海拉康定胺 C。总的来说，这项工作证明了海拉克林二胺结构的重新分配，并提出了海拉克林二胺和 palauamine 之间这种复杂的立体化学关系是如何在生物合成中产生的问题。
