Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92037, USA.
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA.
Molecules. 2020 Mar 31;25(7):1604. doi: 10.3390/molecules25071604.
Marine Cyanobacteria (blue-green algae) have been shown to possess an enormous potential to produce structurally diverse natural products that exhibit a broad spectrum of potent biological activities, including cytotoxic, antifungal, antiparasitic, antiviral, and antibacterial activities. Here, we report the isolation and structure determination of palstimolide A, a complex polyhydroxy macrolide with a 40-membered ring that was isolated from a tropical marine cyanobacterium collected at Palmyra Atoll. NMR-guided fractionation in combination with MS-based molecular networking and isolation via HPLC yielded 0.7 mg of the pure compound. The small quantity isolated along with the presence of significant signal degeneracy in both the H and C-NMR spectra complicated the structure elucidation of palstimolide A. Various NMR experiments and solvent systems were employed, including the LRHSQMBC experiment that allows the detection of long-range H-C correlation data across 4-, 5-, and even 6-bonds. This expanded NMR data set enabled the elucidation of the palstimolide's planar structure, which is characterized by several 1,5-disposed hydroxy groups as well as a -butyl group. The compound showed potent antimalarial activity with an IC of 223 nM as well as interesting anti-leishmanial activity with an IC of 4.67 µM.
海洋蓝细菌（蓝藻）已被证明具有巨大的潜力，可以产生结构多样的天然产物，这些产物具有广泛的强效生物活性，包括细胞毒性、抗真菌、抗寄生虫、抗病毒和抗菌活性。在这里，我们报告了从帕利姆拉环礁采集的热带海洋蓝细菌中分离和结构确定的 palstimolide A 的情况。NMR 引导的分馏与基于 MS 的分子网络相结合，并通过 HPLC 分离，得到了 0.7 毫克的纯化合物。由于在 H 和 C-NMR 光谱中均存在显著的信号简并性，因此分离出的少量化合物使 palstimolide A 的结构阐明变得复杂。我们采用了各种 NMR 实验和溶剂系统，包括 LRHSQMBC 实验，该实验允许检测跨越 4、5 甚至 6 个键的长程 H-C 相关数据。该扩展的 NMR 数据集使 palstimolide 的平面结构得以阐明，其特征在于几个 1,5-布置的羟基以及 -丁基。该化合物表现出很强的抗疟原虫活性，IC 为 223 nM，并且具有有趣的抗利什曼原虫活性，IC 为 4.67 µM。
